Uma, K and Kishore, R and Balaram, P (1993) Stereochemical Constraints in Peptide Design: Analysis of the Influence of a Disulfide Bridge and an \alpha-Aminoisobutyryl Residue on the Conformation of a Hexapeptide. In: Biopolymers, 33 (6). pp. 865-871.
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The competing effects of a disulfide bridge and an \alpha-aminoisobutyryl residue (Aib) in determining the conformation of a hexapeptide have been investigated, by comparing the cyclic disulfide Boc-Cys-Val-Aib- Ala-Leu-Cys-NHMe | | S-------------------------S and the acylic peptide Boc-Cys ( SBzl) -Val-Aib-Ala-Leu-Cys( SBzl) -NHMe (2). Previously published nmr and crystallographic studies [ R. Kishore, S. Raghothama, and P. Balaram (1987) Biopolymers, Vol. 26, pp. 873-891; I. L. Karle, R. Kishore, S. Raghothama, & P. Balaram, (1988) Journal of the American Chemical Society Vol. 110, pp. 1958-19631 have established an antiparallel \beta-hairpin structure for 1 with a central Aib-Ala \beta-turn. A comparison of nmr data for 1 and 2 in chloroform and dimethylsulfoxide reveals that the acyclic peptide is conformationally labile. Evidence for a 310-helical conformation in CDC13 is obtained from sensitivity of NH chemical shifts to temperature and solvent perturbation and low JHNC.H values. Studies in solvent mixtures establish a conformational transition on going from CDC13 to ( CD3)2SO. The changes in NH nmr parameters, together with the observation of several interresidue C\alpha iH-Ni+lH nuclear Overhauser effects support a conformation having a central \beta-turn with extended arms in (CD3)2SO. A single Aib residue appears to stabilize a helix in apolar solvents, for the acyclic hexapeptide, while the disulfide bridge serves to lock the beta-hairpin conformation.
|Item Type:||Journal Article|
|Additional Information:||Copyright for this article belongs to John Wiley & Sons, Inc.|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||22 Dec 2004|
|Last Modified:||19 Sep 2010 04:17|
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