Rational design of the first small-molecule antagonists of NHERF1/EBP50 PDZ domains

Anand Mayasundari; Antonio M Ferreira; Liwen He; Neeraj Mahindroo; Don Bashford; Naoaki Fujii

doi:10.1016/j.bmcl.2007.12.038

Rational design of the first small-molecule antagonists of NHERF1/EBP50 PDZ domains

Bioorg Med Chem Lett. 2008 Feb 1;18(3):942-5. doi: 10.1016/j.bmcl.2007.12.038. Epub 2007 Dec 23.

Authors

Anand Mayasundari¹, Antonio M Ferreira, Liwen He, Neeraj Mahindroo, Don Bashford, Naoaki Fujii

Affiliation

¹ Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

PMID: 18180157
DOI: 10.1016/j.bmcl.2007.12.038

Abstract

This report describes the first small-molecule antagonists that specifically target the ligand-binding pocket of PDZ domains of NHERF1 multi-functional adaptor protein. Comparison of the peptide sequence homology between the native ligand of NHERF1 PDZ domains and an indole-based non-peptide chemical scaffold allowed the design of a small-molecule antagonist of NHERF1 PDZ domains.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Design*
Humans
Indoles / chemical synthesis*
Indoles / chemistry
Indoles / pharmacology*
Models, Molecular
Molecular Conformation
Molecular Structure
PDZ Domains / drug effects*
Phosphoproteins / antagonists & inhibitors*
Sodium-Hydrogen Exchangers / antagonists & inhibitors*
Structure-Activity Relationship

Substances

Indoles
Phosphoproteins
Sodium-Hydrogen Exchangers
sodium-hydrogen exchanger regulatory factor