Efficient synthesis of a beta-peptide combinatorial library with microwave irradiation.
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.
Murray
Justin K
JK
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Farooqi
Bilal
B
Sadowsky
Jack D
JD
Scalf
Mark
M
Freund
Wesley A
WA
Smith
Lloyd M
LM
Chen
Jiandong
J
Gellman
Samuel H
SH
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
D010446:Peptide Fragments; D019151:Peptide Library; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2