Dss. Jois et al., INHIBITION OF HOMOTYPIC ADHESION OF T-CELLS - SECONDARY STRUCTURE OF AN ICAM-1-DERIVED CYCLIC PEPTIDE, The journal of peptide research, 49(6), 1997, pp. 517-526
The objective of this study was to elucidate the solution conformation
of cyclo-(1,12) ro2-Ser3-Lys4-Va15-Ile6-Leu7-Pro8-Arg9-Gly11-Cys12 (1
) derived from the intercellular adhesion molecule-1 (ICAM-1). Cyclic
peptide 1 inhibits homotypic adhesion of T-cells (Molt-3) mediated by
ICAM-1 and the leukocyte function-associated antigen-1 (LFA-1) on the
surface of T-cells. Cyclic peptide 1 is more potent than is the linear
peptide r3-Lys4-Val5-Ile6-Leu7-Pro8-Arg9-Gly10-Gly11-Cys12 (2) in inh
ibiting homotypic adhesion. The difference in biological activity of p
eptides 1 and 2 may be due to the more stable conformation of cyclic p
eptide 1 compared to linear peptide 2 or because cyclization prevents
the peptide from adopting non-productive conformation. Therefore, conf
ormational studies of cyclic peptide 1 will give a better understandin
g of its biological active conformation. The conformational studies of
cyclic peptide 1 were done by NMR, CD and molecular dynamics simulati
ons. NMR studies indicated that the major conformation of cyclic pepti
de 1 contained trans-configuration at both X-Pro peptide bonds. Type I
beta-turns at Lys4-Val15-Ile6-Leu7 and Leu7-Pro8-Arg9-Gly10 were foun
d in cyclic peptide 1. The C- and N-terminal regions of this peptide w
ere stabilized by antiparallel beta-sheet-like structure with the pres
ence of intramolecular hydrogen bonds. The overall structure of this p
eptide exposed the hydrophobic side chains on one face of the molecule
and the hydrophilic side chains on the other. (C) Munksgaard 1997.