The search for general strategies for inhibiting protein-protein interactions has been stimulated by recognition of the key role they play in virtually every process of living systems. Multiprotein complex assembly and localization by PDZ domain-containing proteins exemplify processes critical to cell physiology and function that are mediated by beta strand association. Here we describe the development of substituted "@-tides," protease-resistant peptidomimetics incorporating conformationally restricted amino acid surrogates that reproduce the hydrogen-bonding pattern and side-chain functionality of a beta strand. The synthetic flexibility and generality of the substituted @-tide design was demonstrated by the synthesis of a panel of ligands for the alpha1-syntrophin PDZ domain. The rational design of a small molecule of unprecedented affinity for the PDZ domain suggests that these peptidomimetics may provide a general method for inhibiting protein-protein interactions involving extended peptide chains.
Beta strand peptidomimetics as potent PDZ domain ligands. Publishing Authors By Initials
Chemical & Substance for Abstract: Beta strand peptidomimetics as potent PDZ domain ligands. Information
Substance Name: syntrophin alpha1
Registry Number: 0
Grant and Affiliation Information for Beta strand peptidomimetics as potent PDZ domain ligands.
AFFILIATION: Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA.
Country: England
AGENCY: United States NIGMS
GRANT: GM55040
ACRONYM: GM
MEDLINETA: Chem Biol
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