Development of Peptidomimetics Targeting IAPsReport as inadecuate




Development of Peptidomimetics Targeting IAPs - Download this document for free, or read online. Document in PDF available to download.

International Journal of Peptide Research and Therapeutics

, Volume 12, Issue 1, pp 21–32

First Online: 03 March 2006Accepted: 28 September 2005 Inhibitor of apoptosis proteins IAPs such as XIAP subvert apoptosis by binding and inhibiting caspases. Because occupation of the XIAP BIR3 peptide binding pocket by Smac abolishes the XIAP–caspase 9 interaction, it is a proapoptotic event of great therapeutic interest. An assay for pocket binding was developed based on the displacement of Smac 7-mer from BIR3. Through the physical and biochemical analysis of a variety of peptides, we have determined the minimum sequence required for inhibition of the Smac–BIR3 interaction and detailed the dimensions and topology of the BIR3 peptide binding pocket. This work describes the structure–activity relationship SAR for peptide inhibitors of Smac-IAP binding.

KeywordsBIR cancer caspases inhibitors of apoptosis protein IAP peptidomimetics protein–protein interaction Smac-DIABLO AbbreviationsAbuα-aminobutyric acid

Alaalanine

BIRbaculovirus IAP repeat

BSAbovine serum albumin

Chgα-cyclohexylglycine

Cpgα-cyclopropylglycine

DICN,N-diisopropylcarbidiimide

DMEMDulbecco’s modified Eagle’s medium

Dmgα,α-dimethylglycine

FPfluorescence polarization

HOBtN-hydroxybenztriazole

HSQcheteronuclear single quantum coherence spectroscopy

HTShigh throughput screening

Hyphydroxyproline

IAPinhibitor of apoptosis protein

Ileisoleucine

Laclactic acid

Leuleucine

Phephenylalanine

Pippipecolic acid

Proproline

SARstructure–activity relationship

Serserine

Smacsecondary mitochondrial activator of caspase

TFAtrifluoroacetic acid

Valvaline

Download fulltext PDF



Author: Sushil K. Sharma - Christopher Straub - Leigh Zawel

Source: https://link.springer.com/



DOWNLOAD PDF




Related documents