Aromatic Interactions In Peptides : Designed Helices And β-Hairpins
Electronic Theses of Indian Institute of Science
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Title |
Aromatic Interactions In Peptides : Designed Helices And β-Hairpins
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Creator |
Mahalakshmi, R
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Subject |
Helices
β-Hairpins Peptide Folding Peptide Design Peptide β-Hairpins Peptide Helices Conus Monile Peptides Tryptophan Residues Monile Peptides β-Helices β -Sheets Peptide Hairpins Biochemistry |
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Description |
Design of complex protein folds requires complete understanding of the stereochemical principles that govern polypeptide chain folding. Extensive studies on design and synthesis of specific secondary structures like β-helices, β -sheets and hairpins have taught us that the unnatural amino acid aminoisobutyric acid (Aib) can be successfully employed for helix nucleation and tight turns of appropriate stereochemistry are facilitated by the use of DPro-Xxx sequences. Availability of such rigid secondary structure scaffolds therefore permits the design of synthetic peptides that can be used as models for investigation of tertiary interactions, primarily that of aromatic residues. Chapter 1 summarizes the present knowledge of peptide design using non-protein amino acids. The chapter also details the unique features of aromatic amino acids, especially tryptophan, and their employment as secondary structure stabilizing elements. Chapters 2-7 contain detailed descriptions of the work carried out on design, synthesis, and structural characterization of designed peptides containing aromatic amino acids. In Chapter 2, the use of aromatic pairs in strand segments of peptide hairpins has been discussed with the results clearly indicating that aromatic interactions at the non-hydrogen bonding position of peptide hairpins contribute to structure stability. In Chapter 3, accommodation of the Leu-Trp-Val segment in helical scaffolds the role of Trp residues in crystallization has been discussed. Chapter 4 outlines the influence of a large number of Trp residues on the preferred backbone conformation, with the studies clearly indicating a preference for helical scaffolds in small peptides. The role of Trp residues at turn regions of peptide hairpins has been discussed in Chapter 5, using examples from both synthetic peptides and from natural peptides containing Pro-Trp segments. The studies suggest that the Pro-Trp segments serve as helix nucleators and disrupt formation of peptide hairpins. The results of this study have been further extended to Conus monile peptides, discussed in Chapter 6. The studies also suggest the role of an aromatic-Pro segment on the cis-trans isomerization of the Xxx-Pro tertiary amide unit. Chapter 7 discusses the contribution of a Cys-His vs Tyr-His pair on strand segment stability in diproline nucleated peptide hairpins. Chapter 8 summarizes the key findings of the work. Chapter 9 lists the references cited in the thesis and the Appendix chapter provides details of experimental techniques used in the study.β |
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Contributor |
Balaram, P
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Date |
2009-04-15T09:38:39Z
2009-04-15T09:38:39Z 2009-04-15T09:38:39Z 2006-06 |
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Type |
Thesis
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Identifier |
http://hdl.handle.net/2005/458
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Language |
en_US
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Relation |
G20316
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