Design, Synthesis and Characterization of New Embelin Derivatives as Potent Inhibitors of X-Linked Inhibitor of Apoptosis Protein.

ChemInform ◽  
2007 ◽  
Vol 38 (13) ◽  
Author(s):  
Jianyong Chen ◽  
Zaneta Nikolovska-Coleska ◽  
Guoping Wang ◽  
Su Qiu ◽  
Shaomeng Wang
Keyword(s):  
Synthesis And Characterization ◽  
Inhibitor Of Apoptosis ◽  
Design Synthesis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

Design, synthesis, and characterization of new embelin derivatives as potent inhibitors of X-linked inhibitor of apoptosis protein

2006 ◽  
Vol 16 (22) ◽  
pp. 5805-5808 ◽  
Author(s):  
Jianyong Chen ◽  
Zaneta Nikolovska-Coleska ◽  
Guoping Wang ◽  
Su Qiu ◽  
Shaomeng Wang
Keyword(s):  
Synthesis And Characterization ◽  
Inhibitor Of Apoptosis ◽  
Design Synthesis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

Genomic Characterization of the Mouse Inhibitor of Apoptosis Protein 1 and 2 Genes

Genomics ◽  
1997 ◽  
Vol 46 (3) ◽  
pp. 495-503 ◽  
Author(s):  
Peter Liston ◽  
Charles Lefebvre ◽  
Wai Gin Fong ◽  
Jian Ying Xuan ◽  
Robert G. Korneluk
Keyword(s):  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Genomic Characterization

scholarly journals Molecular characterization of an inhibitor of apoptosis protein (IAPs) in freshwater pearl mussel, Hyriopsis schlegelii

Bioengineered ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 365-373 ◽  
Author(s):  
Di Wu ◽  
Chengyuan Wang ◽  
Wanchang Zhang ◽  
Kou Peng ◽  
Junqing Sheng ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Inhibitor Of Apoptosis ◽  
Pearl Mussel ◽  
Freshwater Pearl Mussel ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

scholarly journals Cloning and characterization of the rat homologues of the Inhibitor of Apoptosis protein 1, 2, and 3 genes.

BMC Genomics ◽  
2002 ◽  
Vol 3 (1) ◽  
Author(s):  
Martin Holcik ◽  
Charles A Lefebvre ◽  
Keiko Hicks ◽  
Robert G Korneluk
Keyword(s):  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

scholarly journals Design, synthesis and evaluation of inhibitor of apoptosis protein (IAP) antagonists that are highly selective for the BIR2 domain of XIAP

2013 ◽  
Vol 23 (14) ◽  
pp. 4253-4257 ◽  
Author(s):  
Robert J. Ardecky ◽  
Kate Welsh ◽  
Darren Finlay ◽  
Pooi San Lee ◽  
Marcos González-López ◽  
...  
Keyword(s):  
Inhibitor Of Apoptosis ◽  
Design Synthesis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

scholarly journals Molecular Cloning of ILP-2, a Novel Member of the Inhibitor of Apoptosis Protein Family

2001 ◽  
Vol 21 (13) ◽  
pp. 4292-4301 ◽  
Author(s):  
Bettina W. M. Richter ◽  
Samy S. Mir ◽  
Lisa J. Eiben ◽  
Jennifer Lewis ◽  
Stephanie Birkey Reffey ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Inhibitor Of Apoptosis ◽  
Physical Interaction ◽  
Caspase 9 ◽  
Inhibitor Of Apoptosis Protein ◽  
Normal Tissues ◽  
Apoptosis Protein ◽  
Processed Form

ABSTRACT Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian IAP homolog A [MIHA]) is a potent inhibitor of apoptosis and exerts its effects, at least in part, by the direct association with and inhibition of specific caspases. Here, we describe the molecular cloning and characterization of a human gene related to ILP-1, termed ILP-2. Despite high homology to ILP-1, ILP-2 is encoded by a distinct gene, which in normal tissues is expressed solely in testis. In contrast to ILP-1, overexpression of ILP-2 had no protective effect on apoptosis mediated by Fas (also known as CD95) or tumor necrosis factor. However, ILP-2 potently inhibited apoptosis induced by overexpression of Bax or by coexpression of caspase 9 with Apaf-1, and preincubation of cytosolic extracts with ILP-2 abrogated caspase activation in vitro. A processed form of caspase 9 could be coprecipitated with ILP-2 from cells, suggesting a physical interaction between ILP-2 and caspase 9. Thus, ILP-2 is a novel IAP family member with restricted specificity for caspase 9.

scholarly journals Structure-based design, synthesis, and evaluation of the biological activity of novel phosphoroorganic small molecule IAP antagonists

2020 ◽  
Vol 38 (5) ◽  
pp. 1350-1364 ◽  
Author(s):  
Agnieszka Łupicka-Słowik ◽  
Mateusz Psurski ◽  
Renata Grzywa ◽  
Monika Cuprych ◽  
Jarosław Ciekot ◽  
...  
Keyword(s):  
Cancer Cell Line ◽  
Biochemical Properties ◽  
Inhibitor Of Apoptosis ◽  
Binding Motif ◽  
Inhibitory Influence ◽  
Design Synthesis ◽  
Inhibitor Of Apoptosis Protein ◽  
Design And Synthesis ◽  
Apoptosis Protein ◽  
Fluorescence Polarization Assay

Summary One of the strategies employed by novel anticancer therapies is to put the process of apoptosis back on track by blocking the interaction between inhibitor of apoptosis proteins (IAPs) and caspases. The activity of caspases is modulated by the caspases themselves in a caspase/procaspase proteolytic cascade and by their interaction with IAPs. Caspases can be released from the inhibitory influence of IAPs by proapoptotic proteins such as secondary mitochondrial activator of caspases (Smac) that share an IAP binding motif (IBM). The main purpose of the present study was the design and synthesis of phosphorus-based peptidyl antagonists of IAPs that mimic the endogenous Smac protein, which blocks the interaction between IAPs and caspases. Based on the structure of the IAP antagonist and recently reported thiadiazole derivatives, we designed and evaluated the biochemical properties of a series of phosphonic peptides bearing the N-Me-Ala-Val/Chg-Pro-OH motif (Chg: cyclohexylglycine). The ability of the obtained compounds to interact with the binding groove of the X-linked inhibitor of apoptosis protein baculovirus inhibitor of apoptosis protein repeat (XIAP BIR3) domain was examined by a fluorescence polarization assay, while their potential to induce autoubiquitination followed by proteasomal degradation of cellular IAP1 was examined using the MDA-MB-231 breast cancer cell line. The highest potency against BIR3 was observed among peptides containing C-terminal phosphonic phenylalanine analogs, which displayed nanomolar Ki values. Their antiproliferative potential as well as their proapoptotic action, manifested by an increase in caspase-3 activity, was examined using various cell lines.

scholarly journals BRUCE, a Giant E2/E3 Ubiquitin Ligase and Inhibitor of Apoptosis Protein of the trans-Golgi Network, Is Required for Normal Placenta Development and Mouse Survival

2004 ◽  
Vol 24 (21) ◽  
pp. 9339-9350 ◽  
Author(s):  
Kristina Lotz ◽  
George Pyrowolakis ◽  
Stefan Jentsch
Keyword(s):  
Growth Defect ◽  
Inhibitor Of Apoptosis ◽  
Placental Development ◽  
Inhibitor Of Apoptosis Protein ◽  
Complete Inactivation ◽  
Mouse Tissues ◽  
Apoptosis Protein ◽  
Perinatal Lethality ◽  
Golgi Network

ABSTRACT BRUCE is a highly conserved 528-kDa peripheral membrane protein of the trans-Golgi network. Owing to the presence of an N-terminal single baculovirus inhibitor repeat, BRUCE functions as an inhibitor of apoptosis protein and blocks apoptosis when overexpressed. In addition, due to the presence of a C-terminal ubiquitin-conjugating domain, BRUCE can covalently attach ubiquitin to substrates. Here we report the generation and characterization of BRUCE-deficient mice. Complete inactivation of the BRUCE gene resulted in perinatal lethality and growth retardation discernible after embryonic day 14. The growth defect is linked to impaired placental development and may be caused by insufficient oxygen and nutrient transfer across the placenta. Chorioallantoic placentation initiated normally, but the mutant placenta showed an impaired maturation of the labyrinth layer and a significant reduction of the spongiotrophoblast. No evidence for an elevated apoptosis rate was detectable in embryonic and extraembryonic tissues and in knockout fibroblasts. Thus, although BRUCE is broadly expressed in embryonic, extraembryonic, and adult mouse tissues, this bifunctional protein might play a unique role in normal trophoblast differentiation and embryonic survival.

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