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Title: Structure-Activity Based Study of the Smac-Binding Pocket Within the DIR3 Domain of XIAP

Abstract

A small series of peptide mimics was designed and synthesized to contain a heterocyclic ring in place of the potentially labile N-terminal peptide bond of the tetrapeptide containing the Smac-XIAP-binding motif. Two Smac mimics were shown to bind to the BIR3 domain of XIAP with moderate affinity and one displayed increased activity in cells relative to the Smac peptides. The structures of BIR3-XIAP in complex with a Smac peptide and a peptide mimic were solved and analyzed to elucidate the structure-activity relationship surrounding the Smac-binding domain within BIR3-XIAP.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930397
Report Number(s):
BNL-81123-2008-JA
Journal ID: ISSN 0960-894X; TRN: US200904%%677
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: BioOrganic and Medicinal Chemistry Letters; Journal Volume: 15
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; AFFINITY; APOPTOSIS; CRYSTAL STRUCTURE; INHIBITION; PEPTIDES; PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIPS; national synchrotron light source

Citation Formats

Wist,A., Gu, L., Riedl, S., Shi, Y., and McLendon, G.. Structure-Activity Based Study of the Smac-Binding Pocket Within the DIR3 Domain of XIAP. United States: N. p., 2007. Web.
Wist,A., Gu, L., Riedl, S., Shi, Y., & McLendon, G.. Structure-Activity Based Study of the Smac-Binding Pocket Within the DIR3 Domain of XIAP. United States.
Wist,A., Gu, L., Riedl, S., Shi, Y., and McLendon, G.. Mon . "Structure-Activity Based Study of the Smac-Binding Pocket Within the DIR3 Domain of XIAP". United States. doi:.
@article{osti_930397,
title = {Structure-Activity Based Study of the Smac-Binding Pocket Within the DIR3 Domain of XIAP},
author = {Wist,A. and Gu, L. and Riedl, S. and Shi, Y. and McLendon, G.},
abstractNote = {A small series of peptide mimics was designed and synthesized to contain a heterocyclic ring in place of the potentially labile N-terminal peptide bond of the tetrapeptide containing the Smac-XIAP-binding motif. Two Smac mimics were shown to bind to the BIR3 domain of XIAP with moderate affinity and one displayed increased activity in cells relative to the Smac peptides. The structures of BIR3-XIAP in complex with a Smac peptide and a peptide mimic were solved and analyzed to elucidate the structure-activity relationship surrounding the Smac-binding domain within BIR3-XIAP.},
doi = {},
journal = {BioOrganic and Medicinal Chemistry Letters},
number = ,
volume = 15,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}