Solution structure of a biologically active cyclic LDV peptide analogue containing a type II′β-turn mimetic

The solution structure of cyclo-Gly-Leu-Asp-Val-BTD] (BTD=β-turn dipeptide) has been determined by two-dimensional ¹H-NMR (nuclear magnetic resonance) spectroscopy and systematic conformational searching combined with molecular dynamics studies. The structure contains two hydrogen bonds between the Gly and Val residues, and a type I β-turn with Leu and Asp at the (i+ 1) and (i+ 2) positions of the turn. The cyclic compound shows activity in a scintillation proximity assay (SPA) for the inhibition of the interaction between the integrin α₄β₁ and vascular cell adhesion molecule-1 (VCAM-1). The structure-activity relationship of the LDV sequence is discussed. © Munksgaard 1996.