title: A simple and efficient maleimide-based approach for peptide extension with a cysteine-containing peptide phage library.
abstract: Although peptide-based molecules are known to have therapeutic potential, the generation of phage focused libraries to optimize peptides is effort-consuming. A 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, San Diego, CA 92121,USA.
authors.forename: Buyung
authors.initials: B
authors.lastname: Santoso
authors.forename: Son
authors.initials: S
authors.lastname: Lam
authors.forename: Brion W
authors.initials: BW
authors.lastname: Murray
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D003545:Cysteine / Q000737:chemistry* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008301:Maleimides / Q000737:chemistry*; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D008301:Maleimides; D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; C043592:maleimide; D066246:ErbB Receptors; D003545:Cysteine
keywords: Conjugation; CovX body; Epidermal growth factor receptor; Maleimide; Peptide phage display library