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Dispersion Engineering : Negative Refraction and Designed Surface Plasmons in Periodic StructuresRuan, Zhichao January 2007 (has links)
The dispersion property of periodic structures is a hot research topic in the last decade. By exploiting dispersion properties, one can manipulate the propagation of electromagnetic waves, and produce effects that do not exist in conventional materials. This thesis is devoted to two important dispersion effects: negative refraction and designed surface plasmons. First, we introduce negative refraction and designed surface plasmons, including a historical perspective, main areas for applications and current trends. Several numerical methods are implemented to analyze electromagnetic effects. We apply the layer-KKR method to calculate the electromagnetic wave through a slab of photonic crystals. By implementing the refraction matrix for semi-infinite photonic crystals, the layer-KKR method is modified to compute the coupling coefficient between plane waves and Bloch modes in photonic crystals. The plane wave method is applied to obtain the band structure and the equal-frequency contours in two-dimensional regular photonic crystals. The finite-difference time-domain method is widely used in our works, but we briefly discuss two calculation recipes in this thesis: how to deal with the surface termination of a perfect conductor and how to calculate the frequency response of high-Q cavities more efficiently using the Pad\`{e} approximation method. We discuss a photonic crystal that exhibits negative refraction characterized by an effective negative index, and systematically analyze the coupling coefficients between plane waves in air and Bloch waves in the photonic crystal. We find and explain that the coupling coefficients are strong-angularly dependent. We first propose an open-cavity structure formed by a negative-refraction photonic crystal. To illuminate the physical mechanism of the subwavelength imaging, we analyze both intensity and phase spectrum of the transmission through a slab of photonic crystals with all-angle negative refraction. It is shown that the focusing properties of the photonic crystal slab are mainly due to the negative refraction effect, rather than the self-collimation effect. As to designed surface plasmons, we design a structured perfectly conducting surface to achieve the negative refraction of surface waves. By the average field method, we obtain the effective permittivity and permeability of a perfectly conducting surface drilled with one-dimensional periodic rectangle holes, and propose this structure as a designed surface plasmon waveguide. By the analogy between designed surface plasmons and surface plasmon polaritons, we show that two different resonances contribute to the enhanced transmission through a metallic film with an array of subwavelength holes, and explain that the shape effect is attributed to localized waveguide resonances. / QC 20100817
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X-ray Crystallographic Characterization Of Designed Peptides Containing Heterochiral And Homochiral Diproline Segments And Database AnalysisSaha, Indranil 07 1900 (has links)
Understanding the relation between amino acid sequences and protein structures is one of the most important problems in modern molecular biology. However, due to the complexities in the protein structure, this task is really daunting. Hence, understanding the structural features of proteins and the rules of folding is central to the design of novel and more effective biomaterials. With the inception of the de novo design of synthetic mimetics for protein structural elements, the study of designed peptides is a subject of intense current research. The de novo design of polypeptide structures provides insights into the factors that govern the folding of peptides and proteins. The rational design of synthetic peptide models for secondary structural motifs in proteins depends on the ability to control the polypeptide chain stereochemistry. An approach, which seems to be useful, is the introduction of constrained genetically coded amino acids like Proline or the introduction of non-protein constrained amino acids like Aib which are capable of restricting the range of available backbone conformations of the polypeptide chain. The use of such residues would then permit the design of well defined and intended structural motifs like the β-turns which serve as chain reversal areas of the polypeptide chain. Templates incorporating multiple repeats of such conformationally constrained residues would in turn further enhance the choice of conformational parameters for the polypeptide chain towards folding. Crystal structure determination of the oligopeptides by X-ray diffraction gives insight into the specific conformational states, modes of aggregation, hydrogen bond interactions and solvation of peptides. Precise structural analysis and good characterization of geometrical parameters and stereochemical details of these molecules provide valuable inputs for peptide design and are indispensable for exploring strategies to design peptide sequences which serve as synthetic mimics for folding motifs in proteins. Many of the above points have been investigated in this thesis which incorporates study of designed peptides containing heterochiral and homochiral diproline segments followed by protein database analysis.
This thesis reports results of x-ray crystallographic studies of twenty two (22) oligopeptides containing heterochiral or homochiral diproline segments. Apart from the crystal data, protein database analysis has also been carried out to investigate what actually is found in nature. Given in brackets are the compound names used in the thesis for the peptides solved.
1) Piv-DPro-LPro-NHMe ( DPPN ) [C16H27N3O3 ] 2) Piv-DPro-LPro-LVal-OMe ( DPPV ) [C21H35N3O5 . 0.09 H2O] 3) Piv-DPro-LPro-LPhe-OMe ( DPPF ) [C25H35N3O5 . H2O] 4) Piv-DPro-LPro-DAla-OMe ( DPPDA ) [C19H31N3O5] 5) Piv-LPro-DPro-LAla-OMe ( PDPA ) [C19H31N3O5] 6) Piv-DPro-LPro-LVal-NHMe ( DPPVN ) [C21H36N4O4 . H2O] 7) Piv-DPro-LPro-LLeu-NHMe ( DPPLN ) [C22H38N4O4 . 0.34H2O] 8) Piv-DPro-LPro-LPhe-NHMe ( DPPFN ) [C25H36N4O4 . H2O] 9) Piv-DPro-LPro-Aib-NHMe ( DPPUN ) [C20H34N4O4] 10) Piv-DPro-LPro-DAla-NHMe ( DPPDAN ) [C19H32N4O4] 11) Piv-DPro-LPro-DVal-NHMe ( DPPDVN ) [C21H36N4O4 .1.43 H2O] 12) Piv-DPro-LPro-DLeu-NHMe ( DPPDLN ) [C22H38N4O4 . H2O] 13) Piv-LPro-DPro-LAla-NHMe ( PDPAN ) [C19H32N4O4] 14) Piv-LPro-DPro-LVal-NHMe ( PDPVN ) [C21H36N4O4] 15) Piv-LPro-DPro-LLeu-NHMe ( PDPLN ) [C22H38N4O4 . H2O] 16) Piv-LPro-DPro-LVal-OMe ( PDPVO ) [C21H35N3O5 . H2O] 17) Racemic mixture of Piv-DPro-LPro-DVal-NHMe + Piv-LPro-DPro-LVal-NHMe
( PPVVN ) [C21H36N4O4 . 0.74H2O] 18) Racemic mixture of Piv-DPro-LPro-DLeu-NHMe + Piv-LPro-DPro-LLeu-NHMe ( PPLLN ) [C22H38N4O4 . H2O] 19) Racemic mixture of Piv-DPro-LPro-DPhe-NHMe + Piv-LPro-DPro-LPhe-NHMe
( PPFFN ) [C25H36N4O4 . 2 H2O] 20) Piv-LPro-LPro-LPhe-OMe ( PPFO ) [C25H35N3O5 . 0.5 H2O] 21) Piv-LPro-LPro-LVal-NHMe ( PPVN ) [C21H36N4O4 . H2O] 22) Piv-LPro-LPro-Aib-NHMe ( PPUN ) [C20H34N4O4. H2O]
Results from the X-ray crystallographic analysis of the above peptides provided substantial information regarding role of diproline templates on the folding of the polypeptide chain.
The thesis is divided into the following eight chapters :
Chapter 1 gives a general introduction to the stereochemistry of polypeptide chains and the secondary structure classification: helices, β-sheets and β-turns. This section also provides a brief overview of the use of non standard and D-amino acids into peptide design. Discussions on DProline, puckering states of the Proline ring, diproline segments and racemic mixtures of peptides are also presented. A brief discussion on X-ray diffraction and solution to the phase problem is also given.
Chapter 2 describes the structural characterization in crystals of the five following designed peptides: Piv-DPro-LPro-NHMe (DPPN), Piv-DPro-LPro-Xxx-OMe [Xxx = LVal (DPPV); LPhe (DPPF); DAla (DPPDA)] and Piv-LPro-DPro-LAla-OMe (PDPA) containing the heterochiral diproline segment with an aim towards understanding the directive influence of
short range interaction on polypeptide folding. Except PDPA, in all the structures, a type II’ β-turn was observed at the DPro-LPro segment with the formation of a 4→1 intramolecular hydrogen bond between the atoms of the polypeptide backbone. In PDPA, the expected type II β-turn occurred at the LPro-DPro segment. Thus, the DPro-LPro segment preferably adopts a
type II’ β-turn conformation when present at the C-terminus which is mimicked by the methyl ester group. The use of pivalyol group at the N-terminus is to ensure the trans geometry of the peptide bond between pivalyol and the first Proline.
Crystal parameters
DPPN: C16H27N3O3; P21; a = 10.785(1) Å, b = 15.037(1) Å, c = 11.335(1) Å; β = 109.96(1)°;
Z = 4; R = 0.0388, wR2 = 0.1047.
DPPV: C21H35N3O5 . 0.09 H2O; P212121; a =10.676(1) Å, b = 16.608(1) Å, c = 39.887(1) Å, Z = 12; R = 0.0688, wR2 = 0.1701.
DPPF: C25H35N3O5 . H2O; P21; a = 9.538(1) Å, b = 10.367(1) Å, c = 13.102(1) Å; β = 93.04(1) °; Z = 2; R = 0.0504, wR2 = 0.1455.
DPPDA: C19H31N3O5; P21; a = 11.269(1) Å, b = 9.945(1) Å, c = 18.550(2) Å; β = 97.46(1)°; Z = 4; R = 0.0563, wR2 = 0.1249.
PDPA: C19H31N3O5; P212121; a = 9.043(1) Å, b = 10.183(2) Å, c = 23.371(1) Å; Z = 4; R = 0.0753, wR2 = 0.1603.
Chapter 3 describes the crystal structures of the four following designed peptides containing the heterochiral diproline segment followed by a L-residue or an achiral amino acid residue like Aib : Piv-DPro-LPro-Xxx-NHMe [Xxx = LVal (DPPVN); LLeu (DPPLN); LPhe (DPPFN) and Aib (DPPUN)]. In the first three peptides the DPro-LPro segennt adopts a type II’ β-turn conformation with the formation of a type I β-turn at the LPro-Xxx segment. The peptide backbone overall therefore adopts a consecutive β-turn structure. When the L-amino acids at the C-terminus are replaced by the achiral amino acid Aib, the overall folded structure adopted by the peptide backbone still remains unchanged with the formation of a consecutive
β-turn. All the structures are stabilized by two intramolecular 4→1 hydrogen bonds between the C=O group and the nitrogen atom of the polypeptide backbone.
Crystal parameters
DPPVN: C21H36N4O4 . H2O; P21; a = 9.386(1) Å, b = 12.112(1) Å, c = 10.736(1) Å; β = 99.53(1) °; Z = 2; R = 0.0528, wR2 = 0.1337.
DPPLN: C22H38N4O4 . 0.34H2O; P21; a =9.231(1) Å, b = 17.558(1) Å, c = 15.563(1) Å; β = 91.94(1) °; Z = 4; R = 0.0555, wR2 = 0.1422.
DPPFN: C25H36N4O4 . H2O; P212121; a = 10.473(1) Å, b = 15.980(1) Å, c = 15.994(1) Å; Z = 4; R = 0.0620, wR2 = 0.1826.
DPPUN: C20H34N4O4; P212121; a = 10.571(2) Å, b = 11.063(1) Å, c = 18.536(1) Å; Z = 4; R = 0.0578, wR2 = 0.1256.
Chapter 4 describes the crystal structures of the seven designed peptides containing
heterochiral diproline segment. Three of these contain sequences of the type DPro-LPro-DXxx [DXxx = DAla (DPPDAN); DVal (DPPDVN); DLeu (DPPDLN)] and three contains the enantiomeric peptides of the ones that are mentioned earlier in sequences of the type LPro-DPro-LXxx [LXxx = LAla (PDPAN); LVal (PDPVN); LLeu (PDPLN)]. In order to investigate the effect of the C-terminal protecting group, a final peptide Piv-LPro-DPro-LVal-OMe (PDPVO) was crystallographically characterized. All the peptides containing the DXxx residues adopted different backbone conformations. For DAla, a structure simultaneously having a β-turn and an α-turn was obtained which is the first example in designed peptides of an isolated α-turn. In the case of DVal, an open / extended structure devoid of any intramolecular hydrogen bonding was obtained whereas for DLeu, type II β-turn occurred at the LPro-DLeu segment instead of the expected type II’ turn at the DPro-LPro segment. In the case of enantiomeric peptides, all the three peptides adopted folded structures with exact mirror image conformation being generated for LAla and nearly identical mirror image conformation in the case of LLeu. The enantiomeric peptide of DVal which contained LVal residue following the diproline segment also adopted a folded conformation with the
formation of type II β-turn at the LPro-DPro segment as expected. X-ray crystallographic characterization of PDPVO resulted in the peptide adopting an overall extended / open structure. Thus, the chirality of the C-terminal residue seems to have a profound effect on the conformation of the heterochiral diproline segments. The role of the C-terminal protecting group cannot also be undermined.
Crystal parameters
DPPDAN: C19H32N4O4; P1; a = 5.964(1) Å, b = 9.354(1) Å, c = 9.961(1) Å; α = 75.44(1), β = 78.90(1) °, γ = 77.04(1); Z = 1; R = 0.0728, wR2 = 0.1528.
DPPDVN : C21H36N4O4 .1.43 H2O; P212121; a = 8.744(8) Å, b = 11.609(1) Å, c = 23.577(2)
Å; Z = 4; R = 0.0625, wR2 = 0.1856.
DPPDLN : C22H38N4O4 . H2O; P212121; a = 10.531(3) Å, b = 11.659(3) Å, c = 20.425(6) Å; Z = 4; R = 0.0444, wR2 = 0.1239.
PDPAN: C19H32N4O4; P1; a = 5.964(1) Å, b = 9.354(2) Å, c = 9.961(2) Å; α = 75.44(1), β = 78.90(1) °, γ = 77.04(1); Z = 1; R = 0.0745, wR2 = 0.1572.
PDPVN : C21H36N4O4; P212121; a = 9.743(1) Å, b = 11.423(1) Å, c = 21.664(3) Å; Z = 4; R = 0.0803, wR2 = 0.1899.
PDPLN : C22H38N4O4 . H2O; P212121; a = 10.462(4) Å, b = 11.572(4) Å, c = 20.262(7) Å; Z = 4; R = 0.0968, wR2 = 0.2418.
PDPVO : C21H35N3O5 . H2O; P212121; a = 8.784(4) Å, b = 11.587(5) Å, c = 23.328(1) Å; Z = 4; R = 0.0888, wR2 = 0.1465.
Chapter 5 describes the crystal structures of the three designed peptides containing racemic mixtures [Racemic mixture of Piv-DPro-LPro-DVal-NHMe + Piv-LPro-DPro-LVal-NHMe (PPVVN); Racemic mixture of Piv-DPro-LPro-DLeu-NHMe + Piv-LPro-DPro-LLeu-NHMe (PPLLN); Racemic mixture of Piv-DPro-LPro-DPhe-NHMe + Piv-LPro-DPro-LPhe-NHMe (PPFFN)] having the heterochiral diproline segment in their sequences and three peptides having a homochiral diproline segment [Piv-LPro-LPro-LPhe-OMe (PPFO); Piv-LPro-LPro-LVal-NHMe (PPVN); Piv-LPro-LPro-Aib-NHMe (PPUN)]. The inability of the pure enantiomers to crystallize in the case of Phe (chapter 4) invoked the use of peptide racemates for obtaining a crystal state conformation for the said compound. In all the cases, the L-enantiomer of Xxx crystallized in the asymmetric unit. A type II β-turn was obtained in the case of PPVVN at the LPro-DPro segment and a type II’ β-turn was obtained for PPLLN at the DPro-LLeu segment. in the case of Phe, an open structure devoid of any intermolecular hydrogen bonding an very similar to DPPDVN (chapter 4) was obtained. In the case of homochiral diproline segment containing peptides, PPFO crystallized with two molecules in the asymmetric unit, both of which adopted a type VIA1 hydrogen bonded β-turn conformation with a cis peptide bond between the diproline segment. In the case of Valine (PPVN) however, a structure devoid of any intramolecular hydrogen bonding was obtained. In the final peptide PPUN, a type II β-turn conformation is observed at the LPro-Aib segment. The analysis revealed that the hydration of the peptide can cause dramatic changes in its backbone conformation. In homochiral LPro-LPro sequences, the tendency to form hydrogen bonded turns competes with the formation of semi-extended polyproline structures. The results also emphasize the subtle role of sequence effects in modulating the conformations of short, constrained peptide segments. The possibility of trapping distinct conformational segments of the diproline segments in crystals by generating racemic centro-symmetric crystals in which packing effects may be appreciably different from those observed in the crystals of individual pure enantiomeric peptides has been clearly exploited in this chapter to obtain a crystal in the case of Phe. These results suggest that the energetic differences between these states is small. Conformational choice can therefore be readily influenced by environmental and sequence effects. Crystal parameters PPVVN: C21H36N4O4 . 0.74H2O; C2/c; a = 36.667(17) Å, b = 10.092(5) Å, c = 13.846(6) Å; β = 107.27(1) °; Z = 8; R = 0.1317, wR2 = 0.3141. PPLLN: C22H38N4O4 . H2O; P21/c; a = 10.555(1) Å, b = 11.687(1) Å, c = 20.108(2) Å; β = 95.47(1) °; Z = 4; R = 0.0761, wR2 = 0.2034. PPFFN: C25H36N4O4 . 2 H2O; P21/c; a = 8.883(5) Å, b = 18.811(10) Å, c = 16.033(9) Å; β = 96.28(1) °; Z = 4; R = 0.1218, wR2 = 0.2848. PPFO : C25H35N3O5 . 0.5 H2O; P212121; a = 10.199(1) Å, b = 20.702(2) Å, c = 23.970(2) Å; Z = 8; R = 0.0716, wR2 = 0.1901.
PPVN : C21H36N4O4 . H2O; P212121; a = 9.454(1) Å, b = 11.119(1) Å, c = 23.021(2) Å; Z = 4;
R = 0.0551, wR2 = 0.1587.
PPUN: C20H34N4O4. H2O; P21; a = 6.276(1) Å, b = 14.011(2) Å, c = 12.888(1) Å; β =
96.80(1) °; Z = 2; R = 0.0475, wR2 = 0.1322.
Chapter 6 describes the pyrrolidine ring puckering states of the Proline residue present in diproline segments in the peptides solved in this thesis, the Cambridge structural database
(CSD) [only acyclic diproline containing peptides have been taken into account] and in a non-redundant dataset of proteins in the Protein Data Bank (PDB). The five membered pyrrolidine ring of Proline can be best characterized in terms of the following five endocyclic torsion
angles χ1, χ2, χ3,χ4 and θ. Using various values of these endocyclic torsion angles the following puckering states were identified : [1] Cγ-exo (A) [2] Cγ-endo (B) [3] Cβ-exo (C) [4] Cβ-endo (D) [5] Twisted Cγ-exo-Cβ-endo (E) [6] Twisted Cγ-endo-Cβ-exo (F) [7] Planar (G) [8] Cα-distorted (H) [9] Twisted Cβ-exo-Cα-endo (I) [10] Cδ-endo (K) [11] N-distorted (L) [12] Twisted Cδ-endo- Cγ-exo (N). In the case of peptides solved in this thesis for heterochiral diproline segments, the Cγ-exo / Cβ-exo (AC) combination turns out to more preferred than the other combinations. The Cγ-endo / Cγ-endo (BB) state is the second most populated state. The overall investigation of Proline rings in peptides show that the states Cγ-exo (A), Cβ-exo
(C) and Twisted Cγ-endo-Cβ-exo (F) are the most preferred states of occurrence of the pyrrolidine ring conformation. In the case of proteins, the overall percentage distribution of various combinations indicates that the AA (Cγ-exo / Cγ-exo), AE (Cγ-exo / Twisted Cγ-exo-Cβ-endo) and FF (Twisted Cγ-endo-Cβ-exo / Twisted Cγ-endo-Cβ-exo) categories are the most preferred combinations. For Proline rings in proteins, the states Cγ-exo (A), Twisted Cγ-exo-Cβ-endo (E) and Twisted Cγ-endo-Cβ-exo (F) are the most preferred states of occurrence of the pyrrolidine ring conformation.
Chapter 7 describes the analysis of diproline segments in a non-redundant dataset of proteins In this chapter, the possible conformational states for the diproline segment (LPro-LPro) found in proteins taken from a non-redundant dataset has been investigated an identified with an emphasis on the cis and trans states for the peptide bond between the diproline segment. The occurrence of diproline segments in type VIA1 turns (cis Pro-Pro peptide bond) and other regular secondary structures like type III β-turns and α-helices has been studied. This has been followed up by the amino acid distribution flanking the diproline segment and the conformation adopted by Xaa-Pro and Yaa-Pro segments in proteins. It is observed that for cis Pro-pro peptide bond, the conformation adopted by the first Proline lies in PII region whereas the second Proline inevitably adopts a conformation in the Bridge region, leading to the formation of the type VIA1 β-turn structure. But in the trans case, the conformation adopted by the first Proline is overwhelmingly populated in the PII (Polyproline) and right-handed α-helical region. For position i+2, the major conformation adopted by Proline is P II and α with a substantial amount of occurrences in Bridge and the C7 (γ-turn) region. The analysis also reveals that the cis-cis configuration of the peptide bond is very rare when considering the diproline segment. With a cis-trans peptide linkage, PII-PII conformation is the most stable and favoured conformation for the Pro-Pro segment in proteins. With trans peptide bond linkage between the Proline residues, α- α and PII-Bridge conformations are equally likely for the diproline segment. The population in trans-cis and cis-trans states are comparable indicating that the energy differences between these states is small. However, trans-trans is the most populated state with a percentage occurrence of 85.43%. The analysis and comparison of conformational states for the Xaa-Pro-Yaa sequence reveals that the Xaa-Pro peptide bond exists preferably as the trans conformer rather than the cis conformer. The same is valid for Pro-Yaa segment, with the cis conformer being populated to even lesser extent. The data shows that α- α, PII-α, PII-PII and extended-PII are the most populated states for Xaa-Pro and Pro-Yaa segments as compared to PII-PII and PII-α and states observed for the Pro-Pro segment.
Chapter 8 describes the analysis of single and multiple β-turns in a non-redundant dataset of proteins. The analysis on β-turns in proteins has shed a new light into the propensity values for amino acid residues at various positions of β-turns which in certain cases have undergone appreciable change in values than previously observed. One of the other notable feature of the analysis is the fact that the data displays a higher occurrence of unprimed β-turns of type I and type II as compared to their primed counterparts of type I’ and type II’ as previously observed. In fact, the results show that type I β-turn is the highest occurring turn both in isolated as well as in consecutive β-turn examples. The analysis of multiple β-turns in proteins has revealed many new categories like the (I,I+1,I+3), (I,I+2,I+3) and combination of turns which can be used for the design of the loops, especially in the case of β-hairpins. Among the multiple turns, double turns occur more frequently than the other consecutive turns like triple and quadruple turns. It is also important to note that the number of examples of a hydrogen bonded turn being followed by a hydrogen bonded turn is very less with type IV turn preceding a primed turn in most of the cases. Thus, the data available from consecutive β-turn analysis and the type-dependent amino acid positional preferences and propensities derived from the present study may be useful for modeling various single and consecutive turns, especially in designing loop regions of β-hairpins.
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Designed β-Hairpin, β-Sheet And Mixed α-β Structures In Synthetic PeptidesDas, Chittaranjan 10 1900 (has links)
Synthetic construction of protein molecules has been widely pursued over the last two decades. A primary goal behind de novo protein design has been to build minimal systems by capturing the essential features of protein structures. Such minimal models can be used to understand underlying principles governing folding, structure, and function of proteins molecules. Several approaches envisioning successful construction of synthetic proteins have been described over the years, some of them being admirably successful (DeGrado et al, 1999; Richardson et al> 1992; Baltzer, 1998). Specific patterning of polar and apolar residues in synthetic sequences has been widely used to achieve designed polypeptide structures like helix bundles (DeGrado et ah, 1999) and (3-sheets (Smith and Regan, 1997; Lacroix et a/., 1998), with reliance on hydrophobic driving forces for folding. Our laboratory has been pursuing a distinctly alternative approach, that employs stereochemically constrained amino acids to generate specific secondary structures which can then be assembled into composite structures by appropriately chosen linking segments. This approach, which involves linking prefabricated modules of secondary structures can be termed as a "Meccano set" approach to protein design (Balaram, 1992). The studies embodied in the present thesis describe attempts at construction of synthetic polypeptide motifs using the stereochemically directing influence of conformationally constrained amino acid residues, such as DPro or Aib (α-aminoisobutyric acid). This thesis is subdivided into 8 chapters, with Chapter 1 providing a perspective of the field of protein design. Subsequent chapters (2-8) describe studies directed towards the specific goal of construction of polypeptide motifs.
Chapter 2 describes synthesis and conformational characterization of two octapeptides Boc-Leu-Val-Val-DPro-LAla-Leu-Val-Val-OMe (1) and Boc-Leu-Val-Val-DPro-DAla-Leu-Val-Val-OMe (2), designed to investigate the effect of specific β-turn stereochemistry on β-hairpin structures. 500 MHz NMR studies establish that both peptides 1 and 2 adopt predominantly β-hairpin conformations in chloroform and methanol solutions, with interstrand registry established by observation of long-range nuclear Overhauser effects (NOEs). Specific NOEs provide evidence for a type II' β-turn conformation for the DPro-LAla segment in 1, while the NMR data suggest that a type I' DPro-DAla β-turn conformation predominates in the peptide 2. The crystal structure of 1 reveals two independent molecules in the crystallographic asymmetric unit, both of which adopt β-hairpin conformations nucleated by a type II’ β-turn across DPro-LAla and stabilized by 3 cross strand hydrogen bonds. These designed β-hairpins with defined tight turns produce characteristic vibrational circular dichroism (VCD) patterns, demonstrating the utility of VCD as a probe for conformational analysis of β-hairpins.
In Chapter 3, we present conformational analysis on designed β-hairpin sequences incorporating a 'Phe-Phe' residue pair at a non-hydrogen bonding position. Two octapeptides Boc-Leu-Phe-Val-DPro-Gly-Leu-Phe-Val-OMe and Boc-Leu-Phe-Val-DPro-Ala-Leu-Phe-Val-OMe were synthesized and conformationally characterized by 500 MHz NMR spectroscopy. Specific NOEs observed in solution provide conclusive evidence favoring specific orientation effects pertaining to the 'Phe-Phe' pair. The peptides exhibited anomalous electronic CD, which has been explained in terms of aromatic contributions by the side chain chromophores. Interestingly, the VCD patterns obtained for these peptides were almost identical to those obtained for other β-hairpins, described in Chapter 2.
Chapter 4 describes the synthesis and conformational analysis of designed decapeptide sequences with centrally located DPro-Xxx β-trun segments. Two sequences Boc-Met-Leu»Phe-Val'DPro-Ala-Leu-Val-Val-Phe-OMe (1) and Boc-Met-Leu-Val-Val-^ro-Gly-Leu-Val-Val-Phe-OMe (2) were designed to study the effect of chain length elongation, of β-strands, on designed β-hairpin structures. 500 MHz NMR studies establish β-hairpin folds in both these sequences, with strand segments aligned even at the termini of the structures.
Multi-stranded, antiparallel β-sheet structures can be generated by successive placement of β-hairpin sequences in a single polypeptide chain. The successful construction of three stranded β-sheet structures is described in Chapter 5 of this dissertation. A 14-residue peptide Boc-Leu-Phe-Val-DPro-Gly-Leu-Val-Leu-Ala-DPro-Gly-Phe-Val-Leu-OMe (LFV14) was designed such that it is composed of three strand segments linked by two DPro-Gly turn segments. The peptide showed excellent solubility in apolar media, permitting detailed conformational analysis by 500 MHz NMR spectroscopy in organic solvents. Observation of long-range, interstrand NOEs, diagnostic of multiple hairpin structures, provides conclusive evidence for a predominantly populated three stranded β-sheet structure in solution. Extension of this strategy has been described in which an 18-residue peptide, Arg-Gly-Thr-Ile-Lys-DPro-Gly-Val-Thr-Phe-Ala-DPro-Ala-Thr-Lys-Tyr-Gly-Arg, was designed with enhanced solutility in water to probe (β-sheet structure formation in aqueous and mixed aqueous-methanol systems. NMR data provided conclusive evidence in favor of the desired structure being significantly populated in methanol and methanol-water mixtures (50 %, v/v). In water, spectroscopic evidence suggests that the long-range order expected of a three-stranded structure is lost, possibly due to water invading the interstrand hydrogen bonds.
Successful construction of a four-stranded antiparallel β-sheet structure has been
demonstrated in Chapter 6. A 26-residue peptide Arg-Gly-Thr-Ile-Lys»DPro-Gly-Ile-Thr-
Phe-Ala-DPro-Ala-Thr-Val-Leu-Phe-Ala-Val-DPro-Gly-Lys-Thr-Leu-Tyr-Arg was designed to have four strand segments linked by three DPro-Xxx turn segments. The peptide exhibited excellent NMR properties permitting structure determination by analysis of NOE data, which revealed that a four stranded β-sheet structure is indeed populated in methanol. Structural studies on this peptide in mixed methanol-water established that the four stranded β-sheet is appreciably populated at a composition of 50 % (v/v) methanol-water mixture, with the β-sheet structure still detectable even at a composition of 70 % water-30 % methanol. In a completely aqueous environment, the β-sheet structures is significantly disrupted, presumably due to solvent invasion. The nucleating β-turns, however, appear to have retained their structural integrity even in this competitive environment.
Chapter 7 describes the insertion of L-Lactic acid (Lac), a hydroxy acid, into polypeptide helices stabilized by a-aminoisobutyricacid (Aib). This study was undertaken to investigate the effect of hydrogen bond deletion on peptide helices. Crystal structure determination of three oligopeptides containing Lac residues has been performed. Peptide 1, Boc-Val-Ala-Leu-Aib-Val-Lac-Leu-Aib-Val-Ala-Leu-OMe, and peptide 2, Boc-Val-Ala-Leu-Aib-Val-Lac-Leu-Aib-Val-Leu-OMe adopt completely helical conformations in the crystalline state, with the Lac(6) residue comfortably accommodated in the center of a helix. NMR studies of peptide 1 and its all amide analog 4, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe, provide firm evidence for a continuous helical segment in both the cases. In a 14-residue peptide 3, Boc-Val-Ala-Leu-Aib- Val- Ala-Leu- Val- Ala-Leu- Aib-Val-Lac-Leu-OMe, residues Val( 1 )-Leu( 10) adopt a helical conformation, which is terminated by formation of a Schellman motif, with Aib(ll) as the site of chiral reversal. The loss of the hydrogen bond at the C-terminus appears to facilitate the chiral reversal at Aib(l 1).
In the final section of this thesis, Chapter 8, successful construction of a synthetic motif containing two distinct elements of secondary structure, a (β-hairpin and a helix, has been described. The design of a 17-residue peptide Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Gly-Gly-Leu-Phe-Val-DPro-Gly-Leu-Phe-Val-OMe, BH17, is based on a modular approach, in which previously characterized β-hairpin (Leu-Phe-Val-DPro-Gly-Leu-Phe-Val) and helix (Val-Ala-Leu-Aib-Val-Ala-Leu) modules are linked by a Gly-Gly linker. The positioning of the achiral Gly residue at position 8 facilitates termination of the potential helical segment (residues 1-7) by formation of a Schellman motif. Gly(9) is anticipated to be the sole conformationally flexible residue. NMR studies on BH17 indicated the presence of both the helix (residues 1-7) and the β-hairpin (residues 10-17) structures in the sequence, with four major conformational possibilities at the linking segment. Crystal structure determination of BH17 revealed that the two elements of structure are approximately arranged in an orthogonal fashion. The crystal structure validates the original premise that a modular assembly strategy may be viable for the construction of larger synthetic structures.
Chapter 9 summarises the major results of this thesis.
(For formulae, please refer "pdf" format)
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Facilitating Conceptual Change In Learning Rate Of Reaction ConceptsBozkoyun, Yasin 01 September 2004 (has links) (PDF)
The main aim of this study to investigate the effectiveness of conceptual change texts oriented instruction accompanied with analogies over traditionally designed chemistry instruction on overcoming 10th grade students& / #8217 / misconceptions, their understanding of rate of reaction concepts and attitude towards chemistry as a school subject.
56 tenth grade students from two classes of a chemistry course taught by the same teacher in the ATATÜ / RK Anatolian High school, participated in the study. This study was carried out in 2003-2004 spring semester.
There were two groups in the study. Experimental group was instructed with conceptual change texts oriented instruction accompanied with analogies and the control group was instructed by traditionally designed chemistry instruction over a period of four weeks.
To investigate the effect of treatment, Rate of Reaction Concepts Test and Attitude Scale Toward Chemistry as a school subject were administered to all students in both groups at the beginning and end of the treatment. To evaluate students& / #8217 / science process skills, Science Process Skills Test was administered before treatment.
To test the hypothesis of the study ANOVA and ANCOVA were used. The result of the study showed that students in conceptual change texts oriented instruction accompanied with analogies got higher average scores in Rate of Reaction Concepts Test than traditionally designed chemistry instruction. Also, students in experimental group indicated a higher positive attitude toward chemistry as a school subject. In addition, science process skill was a strong predictor for the achievement related to rate of reaction concepts.
Results and strategies that were developed for this study may be used by teachers to reduce and eliminate students& / #8217 / misconceptions about the rate of reaction concepts.
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Conceptual Change Text Oriented Insruction To Facilitate Conceptual Change In Atoms And MoleculesGunay, Baris 01 January 2005 (has links) (PDF)
The main aim of this study to investigate the effectiveness of conceptual change texts oriented instruction accompanied with analogies over traditionally designed chemistry instruction on overcoming 10th grade students&rsquo / misconceptions, their understanding atoms and molecules concepts and attitude towards chemistry as a school subject .
45 tenth grades students from two classes of a chemistry course taught by the same teacher in Elmadag High School prticipated in the study that was carried out in 2004 &ndash / 2005 Fall semester .
Two student groups participated in the study . One of them , called as Experimental
group , was instructed with conceptual change text oriented instruction accompanied with analogies and the other one , called as Control group , was instructed with traditionally designed chemistry instruction over a period of two weeks .
To investigate the effect of the treatment , Atoms and Molecules Concept Test and Attitude Scale Toward Chemistry as a school subject were administrated to all students in both groups at the begining and end of the the treatment . To evaluate students&rsquo / science process skills , Science Process Skills Test was administrated before treatment .
ANCOVA and ANOVA were used to test the hypothesis of the study . The result of the study showed that students instructed with conceptual change text oriented instruction accompanied with analogies gained higher average scores in Atoms and Molecules Concept Test than students instructed by traditionally designed instruction . In addition , students in experiental group indicated a higher positive attitude toward chemistry as a school subject .The results also indicated science process skill was a stronger predictor for the achievement of atoms and molecules concepts.
Strategies that were developed and results obtained for the present study may be used by science teachers to eliminate the students&rsquo / misconceptions about atoms and molecules concepts and provide better conceptual understanding of atoms and molecules.
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Fabrication and characterization of shape memory polymers at small scalesWornyo, Edem 17 November 2008 (has links)
The objective of this research is to thoroughly investigate the shape memory effect
in polymers, characterize, and optimize these polymers for applications in information storage systems.
Previous research effort in this field concentrated on shape memory metals for
biomedical applications such as stents. Minimal work has been done on shape memory poly-
mers; and the available work on shape memory polymers has not characterized the behaviors
of this category of polymers fully. Copolymer shape memory materials based on diethylene
glycol dimethacrylate (DEGDMA) crosslinker, and tert butyl acrylate (tBA) monomer are
designed. The design encompasses a careful control of the backbone chemistry of the materials.
Characterization methods such as dynamic mechanical analysis (DMA), differential
scanning calorimetry (DSC); and novel nanoscale techniques such as atomic force microscopy
(AFM), and nanoindentation are applied to this system of materials. Designed experiments
are conducted on the materials to optimize spin coating conditions for thin films. Furthermore,
the recovery, a key for the use of these polymeric materials for information storage, is
examined in detail with respect to temperature. In sum, the overarching objectives of the
proposed research are to: (i) design shape memory polymers based on polyethylene glycol
dimethacrylate (PEGDMA) and diethylene glycol dimethacrylate (DEGDMA) crosslinkers,
2-hydroxyethyl methacrylate (HEMA) and tert-butyl acrylate monomer (tBA). (ii) utilize
dynamic mechanical analysis (DMA) to comprehend the thermomechanical properties of
shape memory polymers based on DEGDMA and tBA. (iii) utilize nanoindentation and
atomic force microscopy (AFM) to understand the nanoscale behavior of these SMPs, and
explore the strain storage and recovery of the polymers from a deformed state. (iv) study
spin coating conditions on thin film quality with designed experiments. (iv) apply neural
networks and genetic algorithms to optimize these systems.
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Fritz August BreuhausSchmidle, Elisabeth Breuhaus de Groot, Fritz August January 2006 (has links)
Zugl.: Karlsruhe, Univ., Diss., 2005 / CD-ROM enth.: Datenbank
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The Challenge of Designing Gestures for InteractionEriksson, Anette, Svensson, Caroline January 2001 (has links)
The main interfaces for interaction with computers today are; keyboard, mouse and remote control. In order to interact with the presentation software Power Point, the presenter has to focus either on the computer or the buttons on the remote control. By doing this, the presenter often loses the contact with his audience and his or her flow of speech gets interrupted. This project has researched the possibility of using gestures for interaction with Power Point, by using an appliance that detects gestures. The purpose was that the interaction should be possible to realise by software, which we have done an introductory design of. We have focused on assisting presenters when they use Power Point and other applications when delivering presentation. To collect data and get an understanding of presenters, presentations and gestures we have observed presenters in action, done workshops together with future users and tested some gestures in real life. These are methods inspired from approaches such as ethnographic fieldwork and participatory design. During the whole project we have used video recording to collect and save data. To create an understanding and clear picture of what the future software should include UML-diagrams were used. We have separated gestures in two categories; natural and designed. The natural gestures occur naturally during speech and social interaction, while the designed gestures are gestures that you learn to use and express, often to perform a task. We discovered that it was the designed gestures that are best suited for gestural interaction with computer. Since the designed gestures are close to the natural way of gesturing we see them as easier to learn, remember and also more comfortable to use. We think the designed gestures have the potential to become second nature, therefore they are good to use for interaction with computers. Our research work led us to realise a need for an on/off function, to distinguish the designed gestures from the natural ones. By using a gestural interface during a presentation, the presenters can keep the focus on the audience and the message they want to convey. When gestural interfaces become reality they will introduce a paradigm shift in the way that people interact with computers and information. / Anette Eriksson 0457-12196 Caroline Svensson 0410-24148
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X-ray Crystallographic Studies Of Designed Peptides : Characterization Of Helices And B-HairpinsAravinda, S 02 1900 (has links) (PDF)
No description available.
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Design, Synthesis And Conformational Analysis Of Peptides Containing Omega And D-Amino AcidsRaja, K Muruga Poopathi 06 1900 (has links) (PDF)
No description available.
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