Characterization of Helix Terminating Schellman Motifs in Peptides. Crystal Structure and Nuclear Overhauser Effect Analysis of a Synthetic Heptapeptide Helix

The Schellman motif is a widely observed, helix terminating structural motif in proteins, which is achieved by the adoption of a left-handed helical (α L ) conformation by a C-terminus residue. The resulting hydrogen bonding pattern involves 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 helix. The crystal structure of the heptapeptide Boc-Leu-Aib-Val-Gly-Leu-Aib-Val-OMe ( 1 ) reveals a 3 10 -helix terminated by a Schellman motif with Aib(6) adopting an α L - conformation. The crystals are in the space group P 2 1 with a = 9.958(3)Å, b = 20.447(3)Å, c = 11.723 (2)Å, β = 99.74(2)°, and Z = 2. The final R 1 and wR 2 values are 7.2% and 18.9%, respectively, for 1731 observed reflections [ I ≥ 2σ( I )]. A 6 → 1 hydrogen bond between Aib(2)CO- - - -Val(7)NH and a 5 → 2 hydrogen bond between Val(3)CO- - - -Aib(6)NH are observed. An analysis of several α L terminated helical peptides in crystals suggests that the medium range C i α H- - - -N i +3 H [d α N ( i, i +3)] and C i α H- - - -N i +4 H [d α N ( i, i +4)] interproton distances are indeed characteristic of the Schellman motif. NMR studies in CDCl 3 establish retention of the 3 10 -helical conformation with key NOEs demonstrating the persistence of the conformation determined in crystals. The present study demonstrates the identification of the Schellman motif in solution in a synthetic helical peptide.