title: Novel X-linked inhibitor of apoptosis protein inhibitors as probes of apoptosis in biology and medicine.
abstract: 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.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hu
authors.forename: Aihua
authors.initials: A
authors.lastname: Nie
authors.forename: Kate
authors.initials: K
authors.lastname: Welsh
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pinacho Crisóstomo
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhu
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: An
authors.forename: John C
authors.initials: JC
authors.lastname: Reed
authors.forename: Liangren
authors.initials: L
authors.lastname: Zhang
authors.forename: Ziwei
authors.initials: Z
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008967:Molecular Biology / Q000379:methods*; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: C095673:2-azabicyclo(2.2.1)heptane-3-carboxylic acid; D001643:Bridged Bicyclo Compounds; D010455:Peptides; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D011392:Proline