Peptide-mediated conformational changes in bilipeptides: evidence for the occurrence of stretched species

Abstract

Flexible biliverdins covalently bound to tripeptides of the sequence Pro-X-Y exhibit a remarkable tendency to adopt stretched conformations. This contrasts with the behaviour of the great many bilipeptides synthesized so far, preserving the (Z,Z,Z,syn,syn,syn) geometry. The conformational changes induced are strongly solvent dependent and sensitive to the steric requirements of the amino acid constituent X. In biliverdin bis (tripeptides) carrying two peptide entities in close proximity, the latter influence is superimposed by intramolecular peptide–peptide interchain interactions. In these cases chromophore stretching occurs only if the amino acid entity X becomes more bulky. Conformational changes proceed through rotation around the C(5) methine single bond, thus forming (Z,Z,Z,anti,syn,syn) conformers. The outstanding behaviour of Pro-X-Y peptide esters in favouring stretched conformers in poorly hydrogen-bonding solvents is ascribed to the formation of γ-bends. The conclusions drawn rest upon a combinatory evaluation of UV–VIS, CD, and ¹H NMR spectra of 18 biliverdin peptides, including conformationally mobile and rigid bilatriene chromophores.