Le but de ma thèse a été de réaliser de nouveaux composés hybrides constitués de nanotubes de carbone (ou fullerènes) et de nanotubes de peptide. L'approche choisie a consisté à greffer sur des nanotubes de carbone, ou dans un premier temps sur des fullerènes, via des bras espaceurs, des cyclopeptides « de type Ghadiri» conduisant aux nanotubes de peptide. Pour se faire, la synthèse de bras espaceurs a été nécessaire ainsi que leur fixation sur les nanotubes de carbones ou fullerènes. Les cyclopeptides sont constitués d'un nombre pair d'acides aminés (8) alternés D et L s'auto-assemblant en feuillets ß antiparallèles pour conduire à des nanotubes. Des essais de solubilisation du cyclopeptide diacide révèlent l'impossibilité d'utiliser ces composés en synthèse organique, dans la mesure ou ils ne sont pas solubles dans les solvants organiques classiques. Il a fallut ainsi revoir la synthèse en incluant soit le fullerène en cours de synthèse peptidique soit en modifiant les conditions pour permettre une solubilisation du peptide. Les composés synthétisés ont été caractérisés par différentes méthodes notamment en TEM, FT-IR, ATR, microscopie optique, diffusion de la lumière. De nouvelles applications aux peptides de Ghadiri ont été cherchées en imagerie (par encapsulation du Xénon hyperpolarisé dans les cavités). Il a été mis en évidence de nouvelles organisations cristallines des peptides possibles dans des conditions contrôlées à l'aide de contre ions tels que les éléments de la première colonne du tableau périodique (Li, Na, K, Rb, ou Cs). Ces organisations, différentes en fonction du contre ion choisi, ont un caractère fractal remarquable, une organisation cristalline régulière et on observe un réseau de liaisons hydrogène inattendu dans les conditions utilisés.

Nanoscale, conductive wires fabricated from organic molecules have attracted considerable attention in recent years due to their anticipated applications in the next generation of optical and electronic devices. Such highly ordered 1D nanostructures could be made from a number of routes. One route of particular interest is to self-assemble the wires from biomolecules due to the wide range of assembly methods that can be adapted from nature. For example, biomolecules with aromatic motifs can be self-assembled so that good π-π stacking is achieved in the resultant nanostructure. An additional advantage of using biomolecules is that it enables the interface of the electronic materials with biological systems, which is important for many applications, including nerve cell communication and artificial photosynthesis. In this study, nanowires were prepared by the molecular self-assembly of oligopeptides that were coupled to aromatic components. In order to achieve charge transport though the nanowires, it was imperative that the aromatic components were arranged so that there was π-π stacking with very few structural defects. Therefore, enzymes were used to control the formation of the hydogelators which subsequently self-assembled to produce nanowire networks. Two main systems were studied in this thesis.In the first system, hydrogelators were produced from aromatic peptide amphiphiles via the enzymatic hydrolysis of the methyl ester of fluorenylmethoxycarbonyl (Fmoc)-di/tripeptides. These hydrogelators formed nanostructures due to π-π stacking between the Fmoc groups and H-bonding between the peptides. The nanostructures in turn produced macroscale gel networks. The nanostructures were analyzed by wide angle X-ray diffraction and fluorescence spectroscopy. A combination of Fourier transform infra-red (FTIR), Transmission Electron Microscopy (TEM), Cryo-TEM, and Atomic Force Microscopy (AFM) was used to characterize the networks. The charge transport properties of the dried networks were studied using impedance spectroscopy. Fmoc-L₃ was found to assemble into nanotubes whose walls consisted of 3 self-assembled layers and possessed inner and outer diameters of ~ 9 nm and ~ 18 nm, respectively. The Fmoc-L₃ networks were structurally stabile and were electronically conductive under a vacuum. The sheet resistance of the peptide networks increased with relative humidity due to the increasing ionic conductivity. The resistance of the networks was 0.1 MΩ/sq in air and 500 MΩ/sq in vacuum (pressure: 1.03 mbar) at room temperature. The networks had a band gap of between 1 to 4 eV as measured by UV-Vis spectroscopy and the temperature-impedance studies. Possible routes for aligning the Fmoc-L3 networks were studied in an attempt to improve their conductivity in one direction. In particular, the peptides were assembled under an electric field (0 to 3.75 kV/cm). Random networks were produced at low field strengths, whereas a degree of alignment was obtained at a field strength of 3.75 kV/cm. The conductivity of the aligned networks in the direction of alignment was a factor of three times higher than that of the random networks.The second system studied was Fmoc-dipeptide-OMe hydrogels produced by the enzymatic condensation of an Fmoc-amino acid and an amino acid ester. Preliminary results found that Fmoc-SF-OMe assembled into nanosheets, nanoribbons and spherulites, depending on the temperature at which self-assembly occurred. The Fmoc-XY-OMe films possessed an extremely high resistance (1012 Ω).

In this dissertation, molecular simulation techniques are used for the theoretical prediction of nanoscale properties for peptide-based materials. This work is focused on two particular systems: peptide nanotubes formed by cyclic-D,L peptide units and peptide nanotubes formed by phenylalanine dipeptides [-Phe-Phe-]. Mechanical characterization of cyclic peptide nanotubes is a challenging problem due the anisotropy resulting from the nature of their molecular interactions. To address rigorously the thermo-mechanical stability of cyclic peptide nanotubes (CPNTs), a homogeneous deformation method combined with the generalized elasticity theory and molecular dynamics simulations (MD) were used for the calculation of second order anisotropic elastic constants. The results for anisotropic elastic constants, yield behavior and engineering Young’s modulus show remarkable mechanical stability for these materials supporting experiments for the development of their applications. Furthermore, the heat capacity, thermal expansion coefficient and isothermal compressibility were predicted using numerical difference methods and molecular dynamics. In order to understand the transport properties of confined water in cyclic peptide nanotubes, the influence of nanotube diameter was studied and self-diffusion coefficient, dipole correlation functions and hydrogen bond probabilities were calculated via molecular dynamics and statistical mechanics. Enhanced transport and higher diffusion rates for water were obtained in cyclic peptide nanotubes (CPNTs) compared with commonly used biomedical channels like carbon nanotubes (CNTs). The greater transport efficiency in CPNTs is attributed to the hydrophilic character and high hydrogen bonding presence along their tubular structure, versus the hydrophobic core of CNTs. One of the most important opportunities for cyclic peptide nanotubes is their utilization as artificial ion channels in antibacterial applications. Here, molecular dynamics methods were used to investigate the effect of confinement on the transport properties of Na+ and K+ ions under the influence of electric field; the ion mobility, selectivity, radial distribution function, coordination number and effect of temperature were studied and results from simulations proved their ability to transport ions. Additionally, the molecular organization of phenylalanine dipeptides into ordered peptide nanotubes was investigated, a model for the molecular structure of these nanotubes was proposed and optimized through molecular simulations; a helical pattern was found and characterized. Thermal stability results show that phenylalanine dipeptide nanotubes are stable up to about 400K; above this temperature, a significant decrease in hydrogen bonding was observed and the perfect pattern was altered. Findings from this work open new opportunities for research in the area of peptide based materials and provide tools and methods to study these systems efficiently at nanoscale.

Orientador: Prof. Dr. Wendel Andrade Alves / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2016. / Estudou-se a conjugação de micro/nanotubos de L,L-difenilalanina (MNTs-FF) com dois tipos de fluoróforo: hipericina (Hyp) e ftalocianinas de zinco (ZnPc), visando aplicação na terapia fotodinâmica. Foram feitas investigações sobre conjugados contendo hipericina organizados em diferentes arranjos cristalinos, uma fase hexagonal (P61) e outra ortorrômbica (P22121). Os resultados obtidos evidenciam uma maior eficiência na geração de espécies reativas de oxigênio (ROS) quando a hipericina está conjugada com MNTs-FF, sendo essa eficácia observada em ambas as fases, porém com melhor resultado para a fase hexagonal. Como mecanismo, foi proposto que a organização induzida pelas estruturas peptídicas e a disponibilidade de um ambiente hidrofóbico na interface de Hyp/peptídeo são fundamentais para incrementar a geração de ROS. Para os conjugados MNTs-FF com ftalocianinas de zinco, foram analisadas as propriedades morfológicas e estruturais. Com a variação dos grupos protetores dos derivados do glicerol presentes nas regiões periféricas das ZnPcs, a morfologia tubular usualmente observada em MNTs-FF muda drasticamente e passa a ser caracterizada por hastes micrométricas. Analisando sua superfície em estudos de alta resolução por AFM, foi perceptível a formação de camadas de fotossensibilizadores e um incremento substancial de rugosidade. Mesmo com a mudança na morfologia do material, a simetria cristalográfica P61, tradicionalmente encontrada em MNTs-FF não-conjugados, é mantida. Ensaios de toxicidade foram realizados em células tumorais mamárias (MCF-7), revelando que a morte celular é maior quando as ZnPcs estão conjugadas com MNTs-FF. Estudos de citometria identificaram que a principal via de morte celular é necrose, com eficiência de cerca 80% para os conjugados MNTs-FF/ZnPc. Esses achados mostram que essa conjugação aumenta a eficiência na geração de ROS dos fotossensibilizadores (Fs) utilizados nesse trabalho, indicando potencial aplicação desses materiais na terapia fotodinâmica. / It was studied the conjugation of L,L-diphenylalanine micro/nanotubes (MNTs-FF) with two types of fluorophore: hypericin (Hyp) and zinc phthalocyanines (ZnPc), order application in photodynamic therapy. It was made investigations on conjugates containing hypericin organized into different crystalline symmetries, a hexagonal phase (P61) and an orthorhombic phase (P22121). The results obtained here are evidence for higher efficiency in the generation of reactive oxygen species (ROS) when hypericin appears conjugated to MNTs-FF. This improvement is observed for MNT-FFs organized into both phases; however, efficiency is still higher for self-assemblies exhibiting hexagonal symmetry. As a mechanism, it was proposed that organization induced by peptide structures and availability of a hydrophobic environment in the vicinities of Hyp/peptide interfaces are crucial for boosting the generation of ROS. In conjugates formed between MNTs-FF and ZcPcs, structural and morphological properties were analyzed in detail. It was found that, by varying glycerol moieties in the periphery of ZnPcs, the tubular morphology usually observed in MNTs-FF changes dramatically and is then characterized by micrometer-long sticks with faceted surfaces. High-resolution AFM imaging showed the formation of layers of photosensitizers and substantial increment on the surface roughness. In despite these drastic morphological and surface changes, the crystalline arrangement of peptides within the complexes remained into the hexagonal P61 phase usually found in bare MNTs-FF. Cytotoxocity assays performed on tumoral mammary cells (MCF-7) indicated that cell death upon light irradiation is higher when ZnpCs is conjugated to MNTs-FF. Cytometry assays identified that the main mechanism leading to cell death is necrosis, with effectiveness of about 80% for MNTs-FF/ZnPc. These findings show that this conjugation enhances efficiency in ROS generation by the photosinthesizers used in this work, indicating the potential of these materials for photodynamic therapy.

The study of synthetic peptides aid in improving our current understanding of the fundamental principles for the de novo design of functional proteins. The investigation of designed peptides has been instrumental in providing answers to many questions ranging from the conformational preferences of amino acids to the compact folded structures and also in developing tools for understanding the growth and formation of the protein secondary structures (helices, sheets and turns). In addition, the self-assembly of peptides through non-covalent interactions is also an emerging area of growing interest. The design of peptides which can mimic the protein secondary structures relies on the use of stereochemically constrained amino acid residues at select positions in the linear peptide sequences, leading to the construction of protein secondary structural modules like helices, hairpins and turns. The use of non-coded amino acid residues with strict preferences for adopting particular conformations in the conformational space becomes the most crucial step in peptide design strategies. In addition the crystallographic characterization and analysis of the sequences provides the necessary optimization of the design strategies. The crystallographic characterization of designed peptides provides a definitive and conclusive proof of the success of a design strategy. Furthermore, the X-ray structures provide an atomic view of the interactions, both strong and weak, which govern the growth of the crystal. The information on the geometric parameters and stereochemical properties of a series of peptides, through a systematic study, provides the necessary basis for further scientific investigation, like the molecular dynamics and can also aid in improving the force field parameters meant for carrying out molecular simulations. This can be further complemented by constructing biologically active peptide sequences. The focus of this thesis is to characterize crystallographically the conformational and structural aspects of peptide nanotubes and encapsulated water wires and the β-hairpin peptide models of β-sheets. The systematic study of a series of pentapeptide and octapeptide sequences, containing Aib and D-amino acid residues incorporated at strategic positions, establish the conformation and structural properties of designed peptides as mimics of protein secondary structures and hydrophobic tubular peptide channels and close-packed forms. The structures reported in this thesis are given below: 1 Boc-DPro-Aib-Leu-Aib-Val-OMe (DPUL5) C30H53N5O8 2 Boc-DPro-Aib-Val-Aib-Val-OMe (DPUV5a) C29H51N5O8 .(0.5) H2O 3 Boc-DPro-Aib-Val-Aib-Val-OMe (DPUV5b) C27H51N5O8 .(0.17) H2O 4 Boc-DPro-Aib-Ala-Aib-Val-OMe (DPUA5) C27H47N5O8 5 Boc-DPro-Aib-Phe-Aib-Val-OMe (DPUF5) C33H48N5O8 6 Boc-Pro-Aib-DLeu-Aib-DVal-OMe (PUDL5) C30H53N5O8 7 Boc-Pro-Aib-DVal-Aib-DVal-OMe (PUDV5a) C27H51N5O8 .(0.17) H2O 8 Boc-Pro-Aib-DVal-Aib-DVal-OMe (PUDV5b) C27H51N5O8 . 2H2O 9 Boc-Pro-Aib-DAla-Aib-DVal-OMe (PUDA5) C27H47N5O8 10 Boc-Pro-Aib-DPhe-Aib-DVal-OMe (PUDF5) C33H48N5O8 11 Ac-Phe-Pro-Trp-OMe (FPW) C28H32N4O5.(0.33)H2O 12 Boc-Leu-Phe-Val-DPro-Pro-Leu-Phe-Val-OMe (DPLP8) C56H84N8O1 1 .(0.5) H2O 13 Boc-Leu-Phe-Val-DPro-Pro-Leu-Phe-Val-OMe (YDPP8) C56H83N8O12 .(1.5) H2O 14 Boc-Leu-Val-Val-DPro-ψPro-Leu-Val-Val-OMe (PSIP8) C56H84N8O11S1 .(1.5) H2O 15 Boc-Leu-Phe-Val-DPro-Pro-Leu-Phe-Val-OMe (DPPV8) C48H84N8O11 16 Boc-Leu-Phe-Val-DPro-Aib-Leu-Phe-Val-OMe (DPUF8) C57H88N8O11.(1.5) H2O 17 Piv-Pro-ψH,CH3Pro-NHMe (PSPL3) C22H37N3O5S1 18 Boc-Leu-Val-Val-Aib-DPro-Leu-Val-Val-OMe (UDPV8) C47H84N8O11.2(C3H7NO) 19 Boc-Leu-Phe-Val-DPro-Ala-Leu-Phe-Val-OMe (BH1P8) C54H78N8O11.H2O 20 Boc-Leu-Phe-Val-DPro-Aib-Leu-Phe-Val-OMe (DPUFP8) C55H84N8O11. (0.5) H2O 21 Boc-Leu-Phe-Val-DPro-Pro-Leu-Phe-Val-OMe (YDPPP8) C56H83N8O12. (1.5) H2O The crystal structure determination of the peptides presented in this thesis provides a wealth of information on the folding patterns of the sequences, in addition to the characterization of many structural and geometric properties. In particular, the study sheds light on the growth and formation of peptide nanotubes and the structure of encapsulated water wires, and also the structural details of Type I′ and Type II′β-turn nucleated hairpins. The study provides the backbone and side chain conformational parameters of the sequences, highlighting the varied conformational excursions possible in the peptide molecules. The thesis is divided into 6 chapters and one appendix. Chapter 1 gives a general introduction to the stereochemistry of the polypeptide chain, description of backbone torsion angles of α-amino acid residues and the major secondary structures of α-peptides, namely α-helix, β-sheet and β-turns. The basic structural features of helices and sheets are given. A brief introduction to polymorphism and weak interactions is also presented, followed by a discussion on X-ray diffraction and solution to the phase problem. Chapter 2 is divided into two parts. PART 1 describes the crystal structures of a series of eight related enantiomeric peptide sequences (Raghavender et al., 2009; Raghavender et al., 2010). The crystal structures of four sequences with the general formula Boc-DPro-Aib-Xxx-Aib-Val-OMe (Xxx = Ala/Val/Leu/Phe) and the enantiomeric sequences provided a set of crystal structures withdifferent packing arrangements. The structure of the peptide with Xxx = Leu revealed a nanotube formation with the Leu lining the inner walls of channel. The channels were found to be empty. The sequence with Xxx = Val revealed a solvent-filled water channel.Investigation of the water wire structures on the diffraction data collected on the same crystal over a period of time revealed the existence of two different kinds of water wires in thechannels. Comparison with the peptide tubular structures available in the literature and the water structure inside the aquaporin channels are contrasted. Close-packed structures are observed in the case of Xxx=Ala and Phe. The backbone conformations are essentially identical. Enantiomeric sequences also revealed similar structures. Polymorphic forms were observed in the case of DVal(3) containing sequence. One form is observed to have water-filled channels forming a nanotube, as opposed to the close-packed structure in the polymorphic form. Crystal parameters DPUL5: C30H53N5O8; P65; a = b = 24.3673 (9) Å, c = 10.6844 (13) Å; α = β = 90°, γ = 120°; Z = 6; R = 0.0671, wR2 = 0.1446. DPUV5a: C29H51N5O8 .(0.5) H2O; P65; a = b = 24.2920 (13) Å, c = 10.4838 (11) Å; α = β = 90°, γ = 120°; Z = 6; R = 0.0554, wR2 = 0.1546. DPUV5b: C29H51N5O8 .(0.17) H2O; P65; a = b = 24.3161 (3) Å, c = 10.1805 (1) Å; α = β = 90°, γ = 120°; Z = 6; R = 0.0617, wR2 = 0.1844. DPUA5: C27H47N5O8; P212121; a = 12.2403 (8), b = 15.7531 (11) Å, c = 16.6894 (11) Å; Z =4; R = 0.0439, wR2 = 0.1249. DPUF5: C33H48N5O8; P212121; a = 10.3268 (8), b = 18.7549 (15) Å, c = 18.9682 (16) Å; Z = 4; R = 0.0472, wR2 = 0.1325. PUDL5: C30H53N5O8; P61; a = b = 24.4102 (8) Å, c = 10.6627 (7) Å; α = β = 90°, γ = 120°; Z = 6; R = 0.0543, wR2 = 0.1495. PUDV5a: C29H51N5O8 .(0.17)H2O; P61; a = b = 24.3645 (14) Å, c = 10.4875 (14) Å; α = β = 90°, γ = 120°; Z = 6; R = 0.0745, wR2 = 0.1810. PUDV5b: C29H51N5O8. 2H2O; C2; a = 20.7278 (35), b = 9.1079 (15) Å, c = 19.5728 (33) Å; α = γ = 90°, β = 94.207°; Z = 6; R = 0.0659, wR2 = 0.1755. PUDA5: C27H47N5O8; P212121; a = 12.2528 (12), b = 15.7498 (16) Å, c = 16.6866 (16) Å; Z = 4; R = 0.0473, wR2 = 0.1278. PUDF5: C33H48N5O8; P212121; a = 10.3354 (8), b = 18.7733 (10) Å, c = 18.9820 (10) Å; Z = 4; R = 0.0510, wR2 = 0.1526. PART 2 describes the crystallographic characterization of the tubular structure in a tripeptide Ac-Phe-Pro-Trp-OMe (FPW) sequence. The arrangement of the single-file water moleculesin the peptide nanotubes of FPW could be established by X-ray diffraction. In addition, the energetically favoured arrangement of the water wire inside the peptide channels could be modeled by understanding the construction of the peptide nanotube. In particular, the helicalmacrodipole of the peptide nanotube and the water wire dipoles prefer an antiparallel arrangement inside the peptide channels as opposed to parallel arrangements, is established by the classical dipole-dipole interaction energy calculation. In addition, the growth of thenanotubes and the arrangement of the water wires inside the channels could be correlated to the macroscopic dimensions of the crystal by the indexing of the crystal faces and contrasted with the structure of DPUV5. Crystal parameters FPW: C28H32N4O5.(0.33)H2O; P65; a = b = 21.5674 (3) Å, c = 10.1035 (2) Å; α = β = 90°, γ = 120 °; Z = 6; R = 0.0786, wR2 = 0.1771 Chapter 3 provides the crystal structures of five octapeptide β-hairpin forming sequences and a tripeptide containing a modified amino acid, with modification in the side chain (pseudo-proline, ψH,CH3Pro). The parent peptide, Boc-Leu-Phe-Val-DPro-Pro-Leu-Phe-Val-OMe (DPLP8), was observed to form a strong Type II′β-turn at the DPro-Pro segment, and the strand segments adopting a β-sheet conformation. Two molecules were observed in the asymmetric unit, inclined to each other at approximately 70°. Modification in the strand sequence Phe(2) to Tyr(2) also resulted in a hairpin with identical conformation and similar packing arrangement. The difference was in the solvent content. In both the cases the molecules were packed orthogonal with respect to each other, resulting in the formation of ribbon-like structures in three dimensions. The replacement of Phe(2) and Phe(7) with Valine residues, with the retention of DPro-Pro β-turn segment, results in an entiely different packing arrangement (parallel). Modification of Pro(5) residue of the turn segment to Aib(5) and ψPro, also results in the molecules packing orthogonally to each other. The tripeptide with a modified form of ψPro, namely ψH,CH3Pro, resulted in a folded structure with a Type VIa β-turn, with the amide bond between the Pro-ψH,CH3Pro segment adopting a cis configuration (Kantharaju et al., 2009). Crystal parameters DPLP8: C56H84N8O11 .(0.5) H2O; P21; a = 14.4028 (8), b = 18.9623 (11) Å, c = 25.4903 (17) Å, β = 105.674 ° (4); Z = 4; R = 0.0959, wR2 = 0.2251. YDPP8: C56H84N8O12 .(1.5) H2O; P212121; a = 14.4028 (8), b = 18.9623 (11) Å, c = 25.4903 (17) Å, Z = 8; R = 0.0989, wR2 = 0.2064. PSIP8: C57H86N8O11S1.(1.5) H2O; C2; a = 34.6080 (2), b = 15.3179 (10) Å, c = 25.6025 (15) Å, β = 103.593 ° (3); Z = 4; R = 0.0931, wR2 = 0.2259. DPPV8: C48H84N8O11; P1; a = 9.922 (3), b = 11.229 (4) Å, c = 26.423 (9) Å, α = 87.146 (6), β = 89.440° (6), γ = 73.282 (7); Z = 2; R = 0.1058, wR2 = 0.2354. DPUF8: C57H88N8O11 .(1.5) H2O; P21; a = 18.410 (2), b = 23.220 (3) Å, c = 19.240 (3) Å, β = 118.036 ° (4); Z = 4; R = 0.1012, wR2 = 0.2061. PSPL3: C22H37N3O5S1; P31; a = b = 14.6323 (22), c = 10.4359 (22) Å, α = β = 90°, γ = 120°; Z = 3; R = 0.0597, wR2 = 0.1590. Chapter 4 describes the crystal structure and molecular conformation of Type I′β-turn nucleated hairpin. The incorporation of Aib-DPro segment in the middle of Leu-Val-Val strands in the peptide sequence Boc-Leu-Val-Val-Aib-DPro-Leu-Val-Val-OMe results in an obligatory Type I′ turn containing hairpin. The molecular conformation and the packing arrangement of the molecules in the crystal are contrasted with the only Type I′β-hairpin reported in the literature and with a sequence where the turn residues are flipped and strand residues replaced with Phe(2) and Phe(7). Crystal parameters UDPV8: C47H84N8O11.2(C3H7NO); P21; a = 11.0623 (53), b = 18.7635 (89) Å, c = 16.6426 (80) Å, β = 102.369 (8); Z = 2; R = 0.0947, wR2 = 0.1730. Chapter 5 provides the crystal structures of three polymorphic forms of β-hairpins. The structure of BH1P8 provides new insights into the packing of hairpins inclined orthogonally to each other. The two polymorphic forms differ not only in their modes of packing in crystals but also in the strong and weak interactions stabilizing the packing arrangements. The polymorphic forms of DPUFP8 differ only in the content of the solvent in the asymmetric unit and the role it plays in bridging the symmetry related pairs of molecules. The polymorphic form YDPPP8 crystallized in a completely different space group, revealing a completely different mode of packing and also the cocrystallized solvent participating in a different set of interactions. Crystal parameters BH1P8: C54H78N8O11.H2O; P212121; a = 18.7511 (9), b = 23.3396 (11) Å, c = 28.1926 (13)Å; Z = 8; R = 0.1208, wR2 = 0.2898. DPUFP8: C55H84N8O11. (0.5) H2O; P21; a = 18.0950 (4), b = 23.0316 (5) Å, c = 18.6368 (5) Å, β = 117.471 (2); Z = 4; R = 0.0915, wR2 = 0.2096. YDPPP8: C56H83N8O12. (1.5) H2O; P21; a = 14.3184 (8), b = 18.9924 (9) Å, c = 25.1569 (14) Å, β = 105.590 (4); Z = 4; R = 0.1249, wR2 = 0.2929. Chapter 6 provides a comprehensive overview of the β-hairpin peptide crystal structures published in the literature as well as those included in the thesis. The hairpins are classified based on the residues composing the β-strands and the mode of their packing in the crystals. In the crystal structures the hairpins are observed to adopt either a Type II′ or Type I′β-turns. The indexing of the crystal faces of a few representative hairpin peptides crystallographically characterized in this thesis, provides a rational explanation for the preferential growth of the crystals in certain directions, when correlated with the strong directional forces (hydrogen bonding) and weak interactions (van der Waals, aromatic-aromatic) observed in the crystal packing. The insights gained by these studies would be highly valuable in understanding the nucleation and growth of β-hairpin peptides and the formation of β-sheet structures. Appendix I describes the Cambridge Structural Database (CSD) analysis of the conformational preferences of the proline residues found in the peptide crystal structures. The frequency distributions of the backbone φ, ψ and ω and side chain χ1, χ2, χ3, χ4 and θ torsion angles of the proline residues are calculated, tabulated and represented as graphical plots. The correlation between the backbone and endocyclic torsion angles provides for a clear evidence of the role of a particular torsion variable χ2 in deciding the state of puckering. In addition, the endocyclic bond angles also appear to be correlated, relatively strongly, with the χ2 torsion. This provides a geometrical explanation of the factors governing the puckering of the proline ring.