INFLUENCE OF SERINE IN POSITION-I ON CONFORMATION AND DYNAMICS OF REVERSE TURNS

NMR spectroscopy has been employed for the conformational analysis of the cyclic hexapeptide ro(1)-Ala(2)-Ser(3)(Bzl)-Trp(4)-Orn(5)(Z)-Tyr(6 )-) with and without protecting groups on Ser(3) and Orn(5). This pept ide sequence was derived from the active loop sequence of the alpha-am ylase inhibitor Tendamistat (HOE 467). The aim was to investigate the role of serine in position i of a standard beta-turn on the conformati on and stabilization of this turn. Based on distance and torsion const raints from 2D NMR spectroscopic measurements in DMSO-d(6) solution, s tructure refinement was accomplished by restrained molecular dynamics (MD) simulations in vacuo and in DMSO. The analysis of both structures in solution reveals a considerable effect of the unprotected serine s idechain on the adjacent beta-turn conformation. While in the protecte d peptide with Ser(3)(Bzl) a beta II-turn is observed between Trp(4) a nd Orn(5), the deprotected compound reveals a beta I-turn in this regi on. The beta I-turn is stabilized by a backbone-sidechain hydrogen bon d from Orn(5)N(alpha)H to Ser(3)O(gamma). Comparisons with other NMR-d erived solution structures of cyclic model peptides and in some protei n structures from literature reveal a general structural motif in the stabilization of beta I-turns by serine in the i position through back bone-sidechain interactions. (C) Munksgaard 1995.