First interchain peptide interaction detected by ESR in fully synthetic, template-assisted, two-helix bundles

We have designed and synthesized by solution methods two simple two-helix b undles based on a conformationally constrained cyclo-dipeptide template to the side chains of which two short, 2,2,6,6tetramethylpiperidine-1-oxyl-4-a mino-4-carboxylic acid spin-monolabeled. 3(10)-helical peptides are covalen tly tethered. The preferred conformation of the appended chains has been as sessed by FTIR absorption. The conclusions are corroborated by an X-ray dif fraction analysis of one of the terminally blocked pentapeptide tails. For the first time, a solvent-dependent, inter-helix interaction has been monit ored by conventional ESR spectroscopy on fully synthetic peptide systems. H alf-field ESR measurements of these side-chain-substituted templates provid ed an experimental average distance between the two labels that is in good accord with that determined in a molecular modeling study.