Structural characterization of folded pentapeptides containing centrally positioned β(R)Val, γ(R)Val and γ(S)Val residues

Abstract

A cylindrical pore of ~7.5 Å diameter containing a one-dimensional water wire, within the confines of a hydrophobic channel lined with the valine side chain, has been observed in crystals of the peptide Boc-D-Pro-Aib-Val-Aib-Val-OMe (1) (Raghavender et al., 2009, 2010). The synthesis and structural characterization in crystals of three backbone homologated analogues Boc-D-Pro-Aib-β³(R)Val-Aib-Val-OMe (2), Boc-D-Pro-Aib-γ⁴(R)Val-Aib-Val-OMe (3), Boc-D-Pro-Aib-γ⁴(S)Val-Aib-Val-OMe (4) are described. Crystal structures of peptides 2, 3 and 4 reveal close-packed arrangements in which no pore was formed. In peptides 2 and 3 the N-terminus D-Pro-Aib segment adopted conformations closely related to Type II' β-turns, while residues 2-4 form one turn of an αα right-handed C₁₁ helix in 2 and an αγ C₁₂ helix in 3. In peptide 4, a continuous left-handed helical structure was observed with the D-Pro-Aib segment forming a Type III' β-turn, followed by one turn of a left-handed αγ C₁₂ helix.