Natural and non-natural amino-acid side-chain substitutions: affinity and diffraction studies of meditope-Fab complexes.

ABSTRACT: Herein, multiple crystal structures of meditope peptide derivatives incorporating natural and unnatural amino acids bound to the cetuximab Fab domain are presented. The affinity of each derivative was determined by surface plasmon resonance and correlated to the atomic structure. Overall, it was observed that the hydrophobic residues in the meditope peptide, Phe3, Leu5 and Leu10, could accommodate a number of moderate substitutions, but these invariably reduced the overall affinity and half-life of the interaction. In one case, the substitution of Phe3 by histidine led to a change in the rotamer conformation, in which the imidazole ring flipped to a solvent-exposed position. Based on this observation, Phe3 was substituted by diphenylalanine and it was found that the phenyl rings in this va

SUBMITTER: Bzymek KP 

PROVIDER: S-EPMC5101583 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature