TEMPLATE-NUCLEATED ALANINE-LYSINE HELICES ARE STABILIZED BY POSITION-DEPENDENT INTERACTIONS BETWEEN THE LYSINE SIDE-CHAIN AND THE HELIX BARREL

The helicity in water has been determined for several series of alanin e-rich peptides that contain single lysine residues and that are N-ter minally linked to a helix-inducing and reporting template termed Ac-He l(1). The helix-propagating constant for alanine (s(Ala) value) that b est fits the properties of these peptides lies in the range of 1.01-1. 02, close to the value reported by Scheraga and coworkers [Wojcik, J., Altmann, K.-H. & Scheraga, H.A. (1990) Biopolymers 30, 121-134], but significantly lower than the value assigned by Baldwin and coworkers [ Chakrabartty, A., Kortemme, T. & Baldwin, R. L. (1994) Protein Sci. 3, 843-852]. From a study of conjugates Ac-Hel(1)-Ala(n)-Lys-Ala(m)-NH2 and analogs in which the methylene portion of the lysine side chain is truncated, we find that the unusual helical stability of Ala(n)Lys pe ptides is controlled primarily by interactions of the lysine side chai n with the helix barrel and only passively by the alanine matrix. Usin g H-1 NMR spectroscopy, we observe nuclear Overhauser effect crosspeak s consistent with proton-proton contacts expected for these interactio ns.