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 bundles based on a conformationally constrained cyclo-dipeptide template to the side chains of which two short, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid spin-monolabeled, 3 10 -helical peptides are covalently tethered. The preferred conformation of the appended chains has been assessed by FTIR absorption. The conclusions are corroborated by an X-ray diffraction analysis of one of the terminally blocked pentapeptide tails. For the first time, a solvent-dependent, inter-helix interaction has been monitored by conventional ESR spectroscopy on fully synthetic peptide systems. Half-field ESR measurements of these side-chain-substituted templates provided an experimental average distance between the two labels that is in good accord with that determined in a molecular modeling study.