Novel X-linked inhibitor of apoptosis protein inhibitors as probes of apoptosis in biology and medicine

We report here a series of new inhibitors of the X-linked inhibitor of apoptosis protein (XIAP protein) based on the SMAC-tetrapeptide AVPI. The structural novelty of these molecules is the presence of the proline mimetic exo-2-azabicyclo[2.2.1]heptane-3-carboxylic acid, leading to analogs with simi...

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Veröffentlicht in:	Experimental biology and medicine (Maywood, N.J.) N.J.), 2011-02, Vol.236 (2), p.247-251
Hauptverfasser:	Hu, Qi, Nie, Aihua, Welsh, Kate, Pinacho Crisóstomo, Fernando R, Zhu, Xuejun, Li, Zhengxiang, An, Jing, Reed, John C, Zhang, Liangren, Huang, Ziwei
Format:	Artikel
Sprache:	eng
Schlagworte:	Apoptosis Bridged Bicyclo Compounds - metabolism Humans Models, Molecular Molecular Biology - methods Molecular Dynamics Simulation Peptides - chemistry Peptides - metabolism Proline - analogs & derivatives Structure-Activity Relationship X-Linked Inhibitor of Apoptosis Protein - antagonists & inhibitors X-Linked Inhibitor of Apoptosis Protein - metabolism
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Beschreibung
Zusammenfassung:	We report here a series of new inhibitors of the X-linked inhibitor of apoptosis protein (XIAP protein) based on the SMAC-tetrapeptide AVPI. The structural novelty of these molecules is the presence of the proline mimetic exo-2-azabicyclo[2.2.1]heptane-3-carboxylic acid, leading to analogs with similar activity to the natural ligand peptide. The structure–activity relationship and computational docking studies support the convenience of this unnatural amino acid as a building block to develop new peptides or small molecules targeting the XIAP-BIR3 domain.
ISSN:	1535-3702 1535-3699
DOI:	10.1258/ebm.2010.010284