Design and synthesis of a simplified inhibitor for XIAP-BIR3 domain.
Based on tetrapeptide AVPI, we were able to design and synthesize a new simplified scaffold to inhibit the BIR3 domain of the XIAP protein at low micromolar range. The uncomplicated synthesis and the binding activity of the molecule disclosed here represent an attractive alternative to develop new compounds targeting the protein-protein interaction of XIAP/caspase9.
Crisóstomo
Fernando R Pinacho
FR
The Burnham Institute for Medical Research, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
Feng
Yongmei
Y
Zhu
Xuejun
X
Welsh
Kate
K
An
Jing
J
Reed
John C
JC
Huang
Ziwei
Z
D017209:Apoptosis; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D024101:Mitochondrial Proteins; D009842:Oligopeptides / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000008:administration & dosage* / Q000037:antagonists & inhibitors
D051034:Inhibitor of Apoptosis Proteins; D024101:Mitochondrial Proteins; D009842:Oligopeptides; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human