Synthesis and Incorporation into Cyclic Peptides of Tolan Amino Acids and Their Hydrogenated Congeners: Construction of an Array of A-B-loop Mimetics of the C epsilon 3 Domain of Human IgE

Daniel A. Offermann, John E. McKendrick, Jimmy J. P. Sejberg, Bingli Mo, Mary D. Holdom, Birgit A. Helm, Robin J. Leatherbarrow, Andrew J. Beavil, Brian J. Sutton, Alan C. Spivey

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

The disruption of the human immunolobulin E-high affinity receptor I (IgE-Fc epsilon RI) protein-protein interaction (PPI) is a validated strategy for the development of anti asthma therapeutics. Here, we describe the synthesis of an array of conformationally constrained cyclic peptides based on an epitope of the A-B loop within the C epsilon 3 domain of IgE. The peptides contain various tolan (i.e., 1,2-biarylethyne) amino acids and their fully and partially hydrogenated congeners as conformational constraints. Modest antagonist activity (IC50 similar to 660 mu M) is displayed by the peptide containing a 2,2'-tolan, which is the one predicted by molecular modeling to best mimic the conformation of the native A-B loop epitope in IgE.
Original languageEnglish
Pages (from-to)3197 - 3214
Number of pages18
JournalJOURNAL OF ORGANIC CHEMISTRY
Volume77
Issue number7
DOIs
Publication statusPublished - 6 Apr 2012

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