Stereochemistry of Schellman motifs in peptides: crystal structure of a hexapeptide with a C-terminus 6 →1 hydrogen bond

Abstract

The Schellman motif is a widely observed helix terminating structural motif in proteins, which is generated when the C-terminus residue adopts a left-handed helical (α_L) conformation. The resulting hydrogen-bonding pattern involves the formation of an intramolecular 6→1 interaction. This helix terminating motif is readily mimicked in synthetic helical peptides by placing an achiral residue at the penultimate position of the sequence. Thus far, the Schellman motif has been characterized crystallographically only in peptide helices of length 7 residues or greater. The structure of the hexapeptide Boc-Pro-Aib-Gly-Leu-Aib-Leu-OMe in crystals reveal a short helical stretch terminated by a Schellman motif, with the formation of 6 → 1 C-terminus hydrogen bond. The crystals are in the space group P2₁2₁2₁ with a = 18.155(3) Å, b = 18.864(8) Å, c = 11.834(4) Å, and Z = 4 . The final R₁ and wR₂ values are 7.68 and 14.6%, respectively , for 1524 observed reflections [F_o ≥ 3ς(F_o)]. A 6 →1 hydrogen bond between Pro(1)CO · · · Leu(6)NH and a 5 →2 hydrogen bond between Aib(2)CO · · · Aib(5)NH are observed. An analysis of the available oligopeptides having an achiral Aib residue at the penultimate position suggests that chain length and sequence effects may be the other determining factors in formation of Schellman motifs.