title: Efficient synthesis of a beta-peptide combinatorial library with microwave irradiation.
abstract: The predictable relationship between beta-amino acid sequence and folding has inspired several biological applications of beta-peptides. For many such applications, it would be desirable to prepare and screen beta-peptide libraries. However, standard peptide synthesis protocols are not efficient enough to support a library approach for many types of beta-peptides. We recently optimized the solid-phase synthesis of beta-peptides using microwave irradiation, and we have now adapted this approach to synthesis on polystyrene macrobeads. We rapidly prepared a high-quality beta-peptide combinatorial library via a split-and-mix strategy. This library was screened in search of beta-peptide antagonists of the p53-MDM2 protein-protein interaction.
authors.affiliation: Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
authors.forename: Justin K
authors.initials: JK
authors.lastname: Murray
authors.forename: Bilal
authors.initials: B
authors.lastname: Farooqi
authors.forename: Jack D
authors.initials: JD
authors.lastname: Sadowsky
authors.forename: Mark
authors.initials: M
authors.lastname: Scalf
authors.forename: Wesley A
authors.initials: WA
authors.lastname: Freund
authors.forename: Lloyd M
authors.initials: LM
authors.lastname: Smith
authors.forename: Jiandong
authors.initials: J
authors.lastname: Chen
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D002240:Carbohydrate Sequence; D006801:Humans; D008872:Microwaves; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology / Q000528:radiation effects*; D019151:Peptide Library; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors
chemical_list: D010446:Peptide Fragments; D019151:Peptide Library; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2