Stabilization of an alpha-helical conformation in an isolated hexapeptide inhibitor of calmodulin

The conformational properties of two hexapeptides, Ac-LWRILW-NH2 and its D- amino acid counterpart Ac-lwrilw-NH2, identified as calmodulin inhibitors u sing mixture-based synthetic combinatorial library approaches, have been ch aracterised by NMR and CD spectroscopy. The peptides fold into an ce-helica l conformation in aqueous solution. The observed short- and medium-range nu clear Overhauser effects were consistent with the formation of an alpha -he lical structure and a reasonably well-defined set of structures was obtaine d by using restraints from the NMR data in simulated annealing calculations . Analysis of glycine-substitution analogues demonstrated that all the amin o acids that make up the peptide sequence are important for the stabilizati on of the a-helical conformation. ne results suggest that a well-defined se t of interactions is indispensable to allow alpha -helix formation in this short hexapeptide. (C) 2001 John Wiley & Sons, Inc.