Department of Chemistry, Birbeck College, University of London, Gordon House, 29 Gordon Square, London WC1H OPP, U.K.
The Leu-Asp-Val (LDV) sequence is known to recognise integrin receptor sites (Komoryia et al., 1991) vital for cell adhesion. The solution structure of the cyclo-Gly-Leu-Asp-Val-BTD, (BTD Type II' [[beta]]-turn dipeptide; Nagai & Sato, 1985) has been determined by 2D 1H-NMR and systematic conformational searching combined with molecular dynamics studies. The structure forms two hydrogen-bonds between the Gly and Val residues, and contains a type I [[beta]]-turn with Leu and Asp at the (I+1) and (I+2) positions of the turn. The cyclic peptide shows activity in a Scintillation Proximity Assay for the inhibition of the interaction between the integrin [[alpha]]4[[beta]]1 and vascular cell adhesion molecule-1. The structure-activity relationship of the LDV sequence is discussed with a view to the design of novel anti-inflammatory agents. We thank the LINK initiative for support and are grateful to the MRC at Mill Hill and ULIRS for provision of NMR facilities.
Komoryia A., Green L.J., Mervic S.S., Yamada M.J., Yamada K.M. & Humphries M.J. (1991) J. Biol. Chem. 266, 15075.
Nagai U. & Sato K. (1985) Tetrahedron Letters, 26, 647.