title: Maleimide-based method for elaboration of cysteine-containing peptide phage libraries.
abstract: Peptide-based molecules are known to have therapeutic utility, but the generation of phage-focused libraries to optimize peptide properties and functionality is challenging. Genetic approaches are limited to peptide extension on the peptide termini. Current chemical methods are technically challenging and time-consuming. A new chemical method is developed to extend a maleimide-conjugated peptide with a cysteine-containing random peptide phage display library. As a proof of concept, a 15-mer epidermal growth factor receptor (EGFR)-binding peptide was synthesized with a maleimide group at its C-terminus and then conjugated to the cysteine-containing library. After panning and screening, several extended peptides were discovered and tested to have a higher affinity to EGFR. This strategy can have broad utility to optimize pharmacophores of any modalities (peptides, unnatural peptides, drug conjugates) capable of bearing a maleimide group.
authors.affiliation: Pfizer Worldwide Research and Development, 10646 Science Center Dr, San Diego, CA, 92121, USA.
authors.forename: Buyung
authors.initials: B
authors.lastname: Santoso
authors.forename: Brion W
authors.initials: BW
authors.lastname: Murray
mesh_terms: D000818:Animals; D003545:Cysteine / Q000737:chemistry; D066246:ErbB Receptors / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008301:Maleimides / Q000737:chemistry*; D019151:Peptide Library
chemical_list: D008301:Maleimides; D019151:Peptide Library; C043592:maleimide; C512478:EGFR protein, human; D066246:ErbB Receptors; D003545:Cysteine