Backbone side chain interactions in peptides. I. Crystal structures of model dipeptides with the Pro-Ser sequence.

The preferential occurrence of amino-acid residues having short polar side-chain within beta-folded regions of crystallized proteins suggests the existence of some stabilizing interaction involving the side polar function. Three model dipeptides tBuCO-L-Pro-L-Ser-NHMe 1, tBuCO-L-Pro-D-Ser-NHMe 2 in the pure enantiomeric a and racemic b forms, and iPrCO-L-Pro-D-Ser-OMe 3 have been investigated in the solid state by X-ray crystallography. Homo and heterochiral sequences 1 and 2 are folded in the beta I and beta II types, respectively, whereas 3 obviously accommodates an open conformation. Besides the i + 3 leads to i hydrogen bond typical of beta-bends in 1, 2a, and 2b, the Ser NH group in all four crystal structures is a proton donor to the lone orbitals of the Ser O gamma oxygen atom. The result is that the disposition of the Ser C alpha--C beta bond corresponds to the rotamer III (chi 1 congruent to 60 degrees). As shown by the crystal structure of 3, the intra-Ser NH. . .O gamma hydrogen bonding is not restricted to beta-folded Pro-Ser sequences. Therefore, this interaction is not only a stabilizing factor for beta-turns but it is also probably responsible for the already mentioned stability of rotamer III for the Ser C alpha--C beta bond in peptides and protein.