90763-52-3Relevant academic research and scientific papers
Direct18F-Labeling of Biomolecules via Spontaneous Site-Specific Nucleophilic Substitution by F-on Phosphonate Prostheses
Wang, Chao,Zhang, Lei,Mou, Zhaobiao,Feng, Wanru,Li, Zhongjing,Yang, Hongzhang,Chen, Xueyuan,Lv, Shengji,Li, Zijing
supporting information, p. 4261 - 4266 (2021/05/26)
We describe a high radiochemical yield late-stage direct 18F-labeling of bare biomolecules containing common active groups. Spontaneity and site-selectivity are attributed to the remarkably higher rates of nucleophilic substitution reactions on phosphonates than on other electrophiles by F- at various hydrogen bond forms. Rapid access to many medicinally significant 18F-labeled biomolecules is achieved at 21-68% radiochemical yields and 35.9-55.1 GBq μmol-1 molar activities both manually or automatically.
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.
Tuning activity-based probe selectivity for serine proteases by on-resin 'click' construction of peptide diphenyl phosphonates
Serim, Sevnur,Mayer, Susanne V.,Verhelst, Steven H. L.
, p. 5714 - 5721 (2013/09/12)
Activity-based probes (ABPs) are powerful tools for functional proteomics studies. Their selectivity can be influenced by modification of a recognition element that interacts with pockets near the active site. For serine proteases there are a limited numb
Human neutrophil elastase phosphonic inhibitors with improved potency of action
Winiarski, ?ukasz,Oleksyszyn, Józef,Sieńczyk, Marcin
experimental part, p. 6541 - 6553 (2012/09/21)
Herein, we present the synthesis and the measurement of the inhibitory activity of novel peptidyl derivatives of α-aminoalkylphosphonate diaryl esters as human neutrophil elastase inhibitors. Their selectivity against other serine proteases, including porcine pancreatic elastase, chymotrypsin, and trypsin, was also demonstrated. We also describe the preparation of single peptide diastereomers. The most active and selective compound developed possessed a kinact/KI of 2353000 M-1 s -1, which is the most potent irreversible peptidyl inhibitor of human neutrophil elastase reported to date. The peptidyl inhibitors were demonstrated to be stable in PBS buffer and human plasma, as were their complexes with HNE.
Simple phosphonic inhibitors of human neutrophil elastase
Sieńczyk, Marcin,Winiarski, ?ukasz,Kasperkiewicz, Paulina,Psurski, Mateusz,Wietrzyk, Joanna,Oleksyszyn, Józef
supporting information; experimental part, p. 1310 - 1314 (2011/04/16)
Herein, we describe the synthesis and resulting activity of a complex series of α-aminophosphonate diaryl esters as irreversible human neutrophil elastase inhibitors and their selectivity preference for human neutrophil elastase over several other serine proteases such as porcine pancreatic elastase, trypsin, and chymotrypsin. We synthesized and examined the inhibitory potency of several new simple Cbz-protected α- aminoalkylphosphonate diaryl esters that yielded several new HNE inhibitors, where one of the obtained compounds Cbz-ValP(OC6H 4-4-COOMe)2 displayed an apparent second-order inhibition value at 33,015 M-1 s-1.
Towards the identification of unknown neuropeptide precursor-processing enzymes: Design and synthesis of a new family of dipeptidyl phosphonate activity probes for substrate-based protease identification
Sabidó, Eduard,Tarragó, Teresa,Giralt, Ernest
supporting information; experimental part, p. 8350 - 8355 (2011/02/22)
Specific proteolytic processing of inactive precursors is an exquisite cellular mechanism that triggers the activation of numerous physiologic peptides and proteins. This process ensures the generation of biologically active peptides, such as many neurope
New aromatic monoesters of α-aminoaralkylphosphonic acids as inhibitors of aminopeptidase N/CD13
Grzywa, Renata,Sokol, Anna M.,Sieńczyk, Marcin,Radziszewicz, Magdalena,Ko?cio?ek, Beata,Carty, Michael P.,Oleksyszyn, Józef
experimental part, p. 2930 - 2936 (2010/07/04)
A series of new aromatic monoesters of α-aminoaralkylphosphonic acids were synthesized by selective hydrolysis of corresponding aromatic diesters of α-aminoaralkylphosphonic acids. New potential inhibitors of aminopeptidase N/CD13, an enzyme important in tumour angiogenesis, were developed. Some derivatives of the homophenylalanine and norleucine related monoaryl phosphonates displayed higher inhibition potency than corresponding α-aminoaralkylphosphonic acids toward aminopeptidase N/CD13. The effect of one of the new inhibitors on the growth of human PANC-1 and HT-1080 cell lines was examined, either alone or in combination with TNF-α.
Synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters
Sieńczyk, Marcin,Kliszczak, Maciej,Oleksyszyn, Józef
, p. 4209 - 4211 (2007/10/03)
This letter describes the first example of the synthesis of isocyanide derivatives of α-aminoalkylphosphonate diphenyl esters. This method produces the title compounds in high purity and in very good yields. It also permits the generation of an α-aminopho
The most potent organophosphorus inhibitors of leucine aminopeptidase. Structure-based design, chemistry, and activity
Grembecka, Jolanta,Mucha, Artur,Cierpicki, Tomasz,Kafarski, Pawe?
, p. 2641 - 2655 (2007/10/03)
A new class of very potent inhibitors of cytosol leucine aminopeptidase (LAP), a member of the metalloprotease family, is described. The X-ray structure of bovine lens leucine aminopeptidase complexed with the phosphonic acid analogue of leucine (LeuP) wa
Synthesis and bioactivities of 1,3,2-benzodiazaphosphorin-2-carboxamide 2-oxides containing α-aminophosphonate groups
Huang, Junmin,Chen, Ruyu
, p. 97 - 101 (2007/10/03)
In order to search for novel antitumor and antiviral agents with high activity and low toxicity, a series of 1-ethoxycarbonylmethyl-3-ethyl-1,2,3,4-tetrahydro-4-oxo-1, 3,2-benzodiazaphosphorin-2-carboxamide 2-oxides containing α-aminophosphonate groups have been designed and synthesized by a convenient one-pot procedure in good yields. The structures of products were confirmed by 1H NMR, 31P NMR, IR spectra, and elemental analyses. The bioassay results showed that some of them possess excellent anti-tobacco mosaic virus activities and exhibit higher inhibitory effects compared with that of the contrast drug 2,4-dioxyhexahydro-1,3,5-triazine.
