Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004. / Vita. / Includes bibliographical references. / Oligomeric mini-proteins, short peptides with protein-like features, constitute valuable minimal models for the study of oligomeric proteins. Oligomerization is a common feature of cellular proteins that may confer structural and functional advantages. Oligomerization is proposed to have arisen by several evolutionary pathways. The structural characterization of peptide 1, a stable oligomeric mini-protein previously developed in the Imperiali group, was undertaken by X-ray crystallography, as knowledge of the structure would enable the rational design of subsequent generations of BBA oligomers varying in packing and stoichiometry. The structure of peptide 1 could not be solved by direct methods, by molecular replacement with search models derived from the monomeric precursor, or by the introduction of heavy atoms. Two selenomethionine mutants having solution-phase properties comparable to the native were identified. The structures of these two peptides were independently solved via MAD phasing experiments, and the refined structures employed as search models for a molecular replacement solution of 1. The structures of the three peptides are homologous, and constitute the first reported structures of a mixed act/ oligomeric mini-protein. The X-ray crystal structures reveal that the oligomeric BBA motif has a domain-swapped architecture that supports a protein-like and water-exclusive core. The structures elucidate the unique role of unnatural amino acids in conferring native secondary structure in a short peptide sequence (21 residues per monomer). / (cont.) Furthermore, the crystal structures reveal that the stoichiometry of the oligomer is tetrameric, rather than trimeric, as originally proposed. A tetrameric solution-phase stoichiometry for this mini-protein family was confirmed by rigorous analytical ultracentrifugation experiments. Heterooligomeric BBA peptides have been designed and characterized in collaboration with Christina M. Taylor and Professor Amy E. Keating of the MIT Biology Department. Acidic and basic residues were substituted along the inter-monomer interface and specific steric interactions were designed in order to disfavor homoassociation and favor heteroassociation. Heterotetramers comparable to peptide 1 in terms of structure and stoichiometry, and approaching the native homotetramer in terms of stability, have been characterized by a variety of biophysical techniques. / by Mayssam H. Ali. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1995. / Includes bibliographical references (p. 181-188). / by Weining Wang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1996. / Includes bibliographical references. / by Joel David Houmes. / Ph.D.

Thesis (B.S.) Massachusetts Institute of Technology. Dept. of Chemistry, 1950. / MIT copy bound with: Indicators for work with nonpolar solvents / Paul H. Egan. 1950. / Bibliography: leaves 50-51. / by Richard Armand Hebert. / B.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2005. / Vita. / Includes bibliographical references. / My graduate research at MIT has been focused on the development of palladium- or nickel-catalyzed cross-coupling reactions using unactivated alkyl electrophiles (e.g., halides and sulfonates). Although aryl and alkenyl electrophiles have been commonly used in such processes, the utility of alkyl substrates has been underdeveloped, and merits further exploration. We have developed the first palladium-based catalyst that is effective for Negishi couplings of primary alkyl electrophiles. A single protocol (2%Pd₂(dba)₃/8%P(Cyp)₃/NMI in THF/NMP at 80⁰C) can be applied to a broad spectrum of electrophiles, including chlorides, bromides, iodides, and tosylates. Concerning the scope of the nucleophilic components, an array of alkyl-, alkenyl-, and arylzinc halides can be coupled. The process is tolerant of a variety of functional groups, including esters, amides, imides, nitriles, and heterocycles. Furthermore, geometrically- defined alkenylzinc species, generated from titanium-mediated hydrozincation of internal alkynes, can be directly used in the process. Despite the progress in nickel- and palladium-catalyzed C(sp³)-C(sp³) bond formation, the methods had been limited to primary alkyl electrophiles. / (cont.) No doubt, the ability to use more challenging, secondary ones will further augment the usefulness of these metal- catalyzed processes. To this end, we have determined that Ni(cod)₂/s-Bu-Pybox can catalyze room-temperature Negishi couplings of an array of functionalized alkyl bromides and iodides. To the best of our knowledge, this is the first nickel- or palladium- catalyzed cross-coupling procedure for unactivated, [beta]-hydrogen-containing secondary alkyl halides. In addition, preliminary studies using substrate-based probes suggest that the oxidative addition proceeds through a radical pathway. This may explain the unparalleled reactivity of the nickel catalyst. As an extension of the nickel catalysis, we have established that the combination of Ni(cod)₂ and bathophenanthroline can effect Suzuki reactions of secondary halides and organoboronic acids. These organoboron reagents are particularly widely used in the cross-coupling chemistry, owing to their chemical stability, biological non-toxicity, and commercial availability. Again, mechanistic evidence has been collected to support the involvement of organic radicals during the oxidative addition step. / by Jianrong (Steve) Zhou. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references. / In the adaptive immune system of higher organisms, T cells are responsible for detecting infections and mounting a response. It is of great importance that T cells respond accurately to very small traces of pathogenic signal in a background sea of healthy cells, to which mounting an immune response in the absence of viral infection could prove fatal for the organism. T cells detect pathogenic signal through noisy protein interaction networks. The goal of this work is to understand how the noise intrinsic to signal transduction mechanisms is mitigated and in some cases exploited to outperform corresponding deterministic mechanisms. Two broad areas of research are presented in this work: 1). Due to fluctuating conformations of proteins, the rate constants of various chemical reactions are not fixed but fluctuate stochastically throughout the course of a signaling cascade. For modeling purposes, this implies that signal detection is based on samples from a large, continuous-time Markov chain whose rate constants follow their own stochastic process. We seek to understand how this behavior limits the information that a network can transmit, and how these limitations can be mitigated based on the specific network topology, or exploited in biological systems to limit autoimmunity. We develop algorithms to detect and characterize the distribution that rate constants sample from. 2). The topology of very early stages in T cell signaling is critical for mounting an accurate immune response. We explore a mechanism that contrasts with the conventional signaling network topology, that outperforms the original by all metrics considered and explains recent experimental results. We study the role that stochasticity in the dwell time of a T cell at an APC plays in achieving a robust cellular response, and explore models of sequential decision making in the immune system. / by Peter Thill. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1952. / Vita. / Includes bibliographical references. / by David A. Johnson. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1996. / Vita. / Includes bibliographical references (leaves 27-29). / by Jared Verrill Goldstone. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2004. / Includes bibliographical references (p. 189-191). / Considered to be a prototype for e⁻ <--> nuclear interaction in more complex molecules, the Alkaline earth monohalides (MX) have a simple electronic structure which consists of two closed-shell atomic ions (M²⁺ + X) in the ion-core and a non-bonding electron in the outer orbital. Their Rydberg spectra will reveal the Rydberg e⁻ <--> ion-core interaction in the simplest case. This thesis presents the experimental results of Calcium Monofluoride (CaF) in the n* = 17 to 18, v⁺ = 1 autoionizing region, of which the OODR (Optical-Optical Double Resonance) spectra were recorded from its D² [sigma]⁺ intermediate state. Since the predissociation limit of CaF lies only 2,800 cm⁻¹ (n* [approximately] 6.3) below its first ionization potential, it had long been believed that the predissociation of CaF has little effect on the spectra. It is surprising that our observations show that in fact the predissociation of CaF can be important and change the appearance of the spectra in the autoionizing region. In the spectra from the low energy region, the line patterns of core-penetrating states are strong and they repeat in consecutive n*-supercomplexes; however, in the n* = 17 to 18, v⁺ = 1 autoionizing region, the core-penetrating states start to disappear due to predissociation and the non-penetrating states become the dominant spectroscopic feature. / by Jiang Xing. / Ph.D.

Massachusetts Institute of Technology. Dept. of Chemistry. Thesis. 1968. Ph.D. / Vita. / Bibliography: leaves 199-201. / Ph.D.