XIAP is a central apoptosis regulator that inhibits apoptosis by binding to and inhibiting the effectors caspase-3/-7 and an initiator caspase-9 through its BIR2 and BIR3 domains, respectively. Smac protein in its dimeric form effectively antagonizes XIAP by concurrently targeting both its BIR2 and BIR3 domains1. Novel proapoptotic Smac mimics/XIAP inhibitors have been designed, synthesized and characterized in our group. These pseudopeptides, containing the 1-aza-2-oxobicyclo[4.3.0]nonane scaffold, were tested by tr-NOE and STD-NMR experiments2. Here, we show the binding evidence and the epitope mapping for a series of new compounds respect to different fragments of XIAP protein: the STD spectra of selected Smac- mimics suggest different binding interactions with BIR2 and BIR3 domains. So, we are able to design new higher affinity compounds.

A NMR STUDY OF SMAC MIMICS TARGETING BOTH THE BIR2 AND BIR3 DOMAINS IN XIAP PROTEIN / D. Potenza, F. Vasile, L. Belvisi, C. Drago, P. Seneci. ((Intervento presentato al convegno MAGNETIC RESONANCE IN THE LIFE SCIENCES : WHAT’S NEW tenutosi a Montecatini , Lucca nel 2008.

A NMR STUDY OF SMAC MIMICS TARGETING BOTH THE BIR2 AND BIR3 DOMAINS IN XIAP PROTEIN.

D. Potenza
Primo
;
F. Vasile
Secondo
;
L. Belvisi;P. Seneci
Ultimo
2008

Abstract

XIAP is a central apoptosis regulator that inhibits apoptosis by binding to and inhibiting the effectors caspase-3/-7 and an initiator caspase-9 through its BIR2 and BIR3 domains, respectively. Smac protein in its dimeric form effectively antagonizes XIAP by concurrently targeting both its BIR2 and BIR3 domains1. Novel proapoptotic Smac mimics/XIAP inhibitors have been designed, synthesized and characterized in our group. These pseudopeptides, containing the 1-aza-2-oxobicyclo[4.3.0]nonane scaffold, were tested by tr-NOE and STD-NMR experiments2. Here, we show the binding evidence and the epitope mapping for a series of new compounds respect to different fragments of XIAP protein: the STD spectra of selected Smac- mimics suggest different binding interactions with BIR2 and BIR3 domains. So, we are able to design new higher affinity compounds.
NMR ; SMAC ; Ligang-protein interaction
Settore CHIM/06 - Chimica Organica
A NMR STUDY OF SMAC MIMICS TARGETING BOTH THE BIR2 AND BIR3 DOMAINS IN XIAP PROTEIN / D. Potenza, F. Vasile, L. Belvisi, C. Drago, P. Seneci. ((Intervento presentato al convegno MAGNETIC RESONANCE IN THE LIFE SCIENCES : WHAT’S NEW tenutosi a Montecatini , Lucca nel 2008.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/147807
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