The board and long term objective is to study the structure and conformation details of cyclic peptides in the crystalline state using x-ray crystallographic techniques. Many biologically active naturally occuring substances like hormones, toxins, antibiotics and ion transport regulators are or contain cyclic peptide moieties. Synthetic analogs of naturally occuring peptides can be easily synthesized and their conformation and biological activity studied. The conformation of a molecule is intimately related to its biological activity. The study of the conformation of cyclic peptides crystallized under different conditions and comparison of the details with those obtained from other methods could be very valuable in determining the bioactive conformation. The process of cyclization reduces the number of possible conformations available for the linear counterpart. The conformational restrictions imposed by cyclization on the peptide geometry make cyclic peptides excellent models for better understanding the basic principles that regulate peptide conformation and the fundamental conformational properties of proteins. Many of the cyclic molecules also interact with biologically important metal ions. These sever as good models for better understanding the mechanism of ion transfer across the biological membranes and understanding the interaction of these ions with peptides and proteins. In this project, the examination of the structure and conformation of a few synthetic cyclic peptides that are useful as analogs for biologically active molecules using x-ray crystallographic techniques is planned. The conformational details obtained by these studies when compared with those obtained from spectroscopic methods may yield information regarding internal mobility of peptide bond. The conformational information may be of use in designing cyclic peptides to carry out specific biological functions such as ions carriers, antibiotics or other useful drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM022490-14
Application #
3271165
Study Section
Biophysics and Biophysical Chemistry A Study Section (BBCA)
Project Start
1988-01-01
Project End
1993-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
14
Fiscal Year
1988
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Type
Schools of Dentistry/Oral Hygn
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Thomas, L M; Ramasubbu, N; Bhandary, K K (1994) Structural characteristics of diproline: a new crystal form of tBoc-Pro-Pro-OH. Int J Pept Protein Res 44:207-14
Thomas, L M; Ramasubbu, N; Bhandary, K K (1994) Crystal structure of cyclo(Pro-Gly)3:Li complex: a model for ion transport by cyclo(Pro-Gly)3. Biopolymers 34:1007-13
Thomas, L M; Ramasubbu, N; Bhandary, K K et al. (1994) A new class of substituted 1,2,4-triazolo-1,3,4-thiadiazepines. Acta Crystallogr C 50 ( Pt 10):1608-12
Bhandary, K K; Chauhan, V S (1993) Peptide design 3(10)-helical conformation of a linear pentapeptide containing two dehydrophenylalanines, Boc-Gly-delta ZPhe-Leu-delta ZPhe-Ala-NHCH3. Biopolymers 33:209-17
Bharadwaj, A; Singh, M; Bhandary, K et al. (1993) Conformationally constrained formyl methionyl tripeptides: structure-function study of analogs containing alpha,beta-dehydrophenylalanine and dehydroleucine. Pept Res 6:298-307
Chauhan, V S; Bhandary, K K (1992) Crystal structure and conformation of a highly constrained linear tetrapeptide Boc-Leu-dehydro Phe-Ala-Leu-OCH3. Int J Pept Protein Res 39:223-8
Bhandary, K K; Kopple, K D (1991) Conformation of cyclic octapeptides. VI. Structure of cyclo-bis-(-L-alanyl-glycyl-L-prolyl-L-phenylalanyl-) tetrahydrate. Acta Crystallogr C 47 ( Pt 7):1483-7
Bhandary, K K (1991) Conformation of cyclo-bis(-L-valyl-L-proplyl-D-alanyl-), a synthetic cyclic hexapeptide. Acta Crystallogr C 47 ( Pt 6):1280-3
Raj, P A; Soni, S D; Ramasubbu, N et al. (1990) Crystal structure and solution conformation of S,S'-bis(Boc-Cys-Ala-OMe): intramolecular antiparallel beta-sheet conformation of an acyclic cystine peptide. Biopolymers 30:73-85
Bhandary, K K; Senadhi, S E; Prasad, K U et al. (1990) Conformation of a cyclic decapeptide analog of a repeat pentapeptide sequence of elastin: cyclo-bis(valyl-prolyl-alanyl-valyl-glycyl). Int J Pept Protein Res 36:122-7

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