Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions

Naoaki Fujii; Jose J. Haresco; Kathleen A.P. Novak; Robert M. Gage; Nicoletta Pedemonte; David Stokoe; Irwin D. Kuntz; R. Kiplin Guy

doi:10.1016/j.bmcl.2006.10.006

Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions

Naoaki Fujii
, Jose J. Haresco
, Kathleen A.P. Novak
, Robert M. Gage
, Nicoletta Pedemonte
, David Stokoe
, Irwin D. Kuntz
, R. Kiplin Guy

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function.

Original language	English (US)
Pages (from-to)	549-552
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2006.10.006
State	Published - Jan 15 2007
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Drug design
Interaction
NHERF
PDZ domain
Protein-protein

Publisher link

10.1016/j.bmcl.2006.10.006

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title = "Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions",

abstract = "Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function.",

keywords = "Drug design, Interaction, NHERF, PDZ domain, Protein-protein",

author = "Naoaki Fujii and Haresco, \{Jose J.\} and Novak, \{Kathleen A.P.\} and Gage, \{Robert M.\} and Nicoletta Pedemonte and David Stokoe and Kuntz, \{Irwin D.\} and \{Kiplin Guy\}, R.",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions

AU - Fujii, Naoaki

AU - Haresco, Jose J.

AU - Novak, Kathleen A.P.

AU - Gage, Robert M.

AU - Pedemonte, Nicoletta

AU - Stokoe, David

AU - Kuntz, Irwin D.

AU - Kiplin Guy, R.

PY - 2007/1/15

Y1 - 2007/1/15

N2 - Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function.

AB - Novel small molecules were designed to specifically target the ligand-binding pocket of a PDZ domain. Iterative molecular docking and modeling allowed the design of an indole scaffold 10a as a reversible inhibitor of ligand binding. The 10a scaffold inhibited the interaction between MAGI-3 and PTEN and showed cellular activities that are consistent with the inhibition of NHERF-1 function.

KW - Drug design

KW - Interaction

KW - NHERF

KW - PDZ domain

KW - Protein-protein

UR - https://www.scopus.com/pages/publications/33846061735

UR - https://www.scopus.com/pages/publications/33846061735#tab=citedBy

U2 - 10.1016/j.bmcl.2006.10.006

DO - 10.1016/j.bmcl.2006.10.006

M3 - Article

C2 - 17055267

AN - SCOPUS:33846061735

SN - 0960-894X

VL - 17

SP - 549

EP - 552

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 2

ER -

Rational design of a nonpeptide general chemical scaffold for reversible inhibition of PDZ domain interactions

Abstract

UN SDGs

Keywords

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