A Rational Approach for Creating Peptides Mimicking Antibody Binding.

ABSTRACT: This study reports a novel method to design peptides that mimic antibody binding. Using the Knob-Socket model for protein-protein interaction, the interaction surface between Cetuximab and EGFR was mapped. EGFR binding peptides were designed based on geometry and the probability of the mapped knob-sockets pairs. Designed peptides were synthesized and then characterized for binding specificity, affinity, cytotoxicity of drug-peptide conjugate and inhibition of phosphorylation. In cell culture studies, designed peptides specifically bind and internalize to EGFR overexpressing cells with three to four-fold higher uptake compared to control cells that do not overexpress EGFR. The designed peptide, Pep11, bound to EGFR with K_D of 252 nM. Cytotoxicity of Monomethyl Auristatin E (MMAE)

SUBMITTER: Sachdeva S 

PROVIDER: S-EPMC6353898 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature