Backbone side chain interactions in peptides.

The high content of serine in beta-folded regions of proteins may be the consequence of some specific interaction between the peptide backbone and the hydroxyl group of the Ser side-chain. The resolution of the X-ray structures of three peptides with the Pro-Ser sequence protected on both ends by amide and/or ester functions indicates that the Ser NH bond is a proton donating group to the Ser O gamma atom in the solid state. The present study deals with spectroscopic investigations on five Ser-containing model dipeptides with the L-Pro-D-Ser 1, L-Pro-L-Ser 2, L-Ala-L-Ser 3, L-Ser-L-Ala 4 and L-Ser-Gly 5 sequences protected on their N and C-termini by tBuCO and NHMe groups, respectively. The N--H. . .O gamma interaction found in the solid state of 1 and 2 is at least partly retained in solution and its occurrence in X-Ser sequences is fully compatible with beta-folding. The same is not true for Ser-X sequences in which the competition between the typical beta-turn i + 3 leads to i hydrogen bond and the N--H . . . O gamma interaction results in lower contents of beta-folded conformers. Because of this latter interaction, the rotamer III (chi 1 congruent to 60 degrees) is the most frequent disposition of the Ser C alpha--C beta bond in all five derivatives.