65164-80-9Relevant articles and documents
Synthesis of unsymmetrically substituted α-aminoalkylphosphonate esters
Moriarty,Liu,Zhuang,Lenz,Brimfield,Xia
, p. 2763 - 2773 (1995)
The title compounds were designed as haptens for production of monoclonal antibodies as potential catalysts for phosphoryl transfer reactions of phosphates and phosphonates. These haptens conform to the 'bait and switch' model.
Structure-based design, synthesis, and evaluation of the biological activity of novel phosphoroorganic small molecule IAP antagonists
?upicka-S?owik, Agnieszka,Psurski, Mateusz,Grzywa, Renata,Cuprych, Monika,Ciekot, Jaros?aw,Goldeman, Waldemar,Wojaczyńska, El?bieta,Wojaczyński, Jacek,Oleksyszyn, Józef,Sieńczyk, Marcin
, p. 1350 - 1364 (2020/04/24)
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.
Convenient syntheses of novel 1-isothiocyano-alkylphosphonate diphenyl ester derivatives with potential biological activity
Psurski, Mateusz,Pigula, Marta,Winiarski, Lukasz,Oleksyszyn, Jozef,Ciekot, Jaroslaw,Wietrzyk, Joanna
supporting information, p. 5845 - 5847,3 (2020/08/20)
Herein, we describe a convenient method for the syntheses of novel 1-isothiocyano-alkylphosphonate diaryl ester derivatives and their antiproliferative activity. The syntheses are based on dithiocarbamates obtained in situ with the use of carbon disulfide