Abstract
The effect of insertion of lactic acid (Lac) residues into peptide helices has been probed using specifically designed sequences. The crystal structures of 11‐residue and 14‐residue depsipeptides Boc–Val–Val–Ala–Leu–Val–Lac–Leu–Aib–Val–Ala–Leu–OMe (1) and Boc–Val–Ala–Leu–Aib–Val–Ala–Leu–Val–Lac–Leu–Aib–Val–Ala–Leu–OMe (3), containing centrally positioned Lac residues, have been determined. The structure of an 11‐residue peptide Boc–Val–Ala–Leu–Aib–Val–Ala–Leu–Aib–Val–Ala–Leu–OMe (2), analog of a which is an amide previously determined Lac‐containing depsipeptide, Boc–Val–Ala–Leu–Aib–Val–Lac–Leu–Aib–Val–Ala–Leu–OMe I. L. Karle, C. Das, and P. Balaram, Biopolymers, Vol. 59, (2001) pp. 276–289], is also reported. Peptide 1 adopts a helical fold, which is stabilized by mixture of 4→1 and 5→1 hydrogen bonds. Peptide 2 adopts a completely α‐helical conformation stabilized by eight successive 5→1 hydrogen bonds. Peptide 3 appears to be predominately α‐helical, with seven 5→1 hydrogen bonds and three 4→1 interaction interspersed in the sequence. In the structure of peptide 3 in addition to water molecules in the head‐to‐tail region, hydration at an internal segment of the helix is also observed. A comparison of five related peptide helices, containing a single Lac residue, reveals that the hydroxy acid can be comfortably accommodated at interior positions in the helix, with the closest CO…O distances lying between 2.8 and 3.3 Å. © 2002 Wiley Periodicals, Inc. Biopolymers 64: 255–267, 2002