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

Abstract

A cylindrical pore of ∼7.5Å 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 αβ 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.