THE EFFECT OF N-METHYLATION ON HELICAL PEPTIDES

In N-methyl amino acids, the hydrogen of the N-H group is replaced wit h a bulky methyl group. While this change is expected to destabilize h elical structures, the amount of destabilization is not known. Here th e N-methyl group is placed into several positions of the helical pepti des, acetyl-WGG(EAAAR)(4)A-amide and acetyl-WGG(RAAAA)(4)R-amide, and the melting of the peptides followed using CD. When analyzed using a s imple two-state model, the destabilization associated with the H to CH 3 substitution at 0 degrees C is between 0.3 to 1.7 kcal/mole and is p osition dependent. The melting data may also be analyzed using a modif ied form of the Lifson-Roig statistics that should more correctly mode l the helix-coil transition in this small peptide. This analysis fails , however, apparently because the destabilization energy is greater th an the energy that can be attributed to a single residue in this model . (C) 1997 John Wiley & Sons, Inc.