135289-79-1Relevant academic research and scientific papers
Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2
H?u?ler, Daniela,Mangold, Martin,Furtmann, Norbert,Braune, Annett,Blaut, Michael,Bajorath, Jürgen,Stirnberg, Marit,Gütschow, Michael
, p. 8525 - 8535 (2016)
Matriptase-2, a type II transmembrane serine protease, plays a key role in human iron homeostasis. Inhibition of matriptase-2 is considered as an attractive strategy for the treatment of iron-overload diseases, such as hemochromatosis and β-thalassemia. In the present study, synthetic routes to nine dipeptidomimetic inactivators were developed. Five active compounds (41–45) were identified and characterized kinetically as irreversible inhibitors of matriptase-2. In addition to a phosphonate warhead, these dipeptides possess two benzguanidine moieties as arginine mimetics to provide affinity for matriptase-2 by binding to the S1 and S3/S4 subpockets, respectively. This binding mode was strongly supported by covalent docking analysis. Compounds 41–45 were obtained as mixtures of two diastereomers and were therefore separated into the single epimers. Compound 45 A, with S configuration at the N-terminal amino acid and R configuration at the phosphonate carbon atom, was the most potent matriptase-2 inactivator with a rate constant of inactivation of 2790 m?1s?1and abolished the activity of membrane-bound matriptase-2 on the surface of intact cells. Based on the chemotyp of phosphono bisbenzguanidines, the design and synthesis of a fluorescent probe (51 A) by insertion of a coumarin label is described. The in-gel fluorescence detection of matriptase-2 was demonstrated by applying 51 A as the first activity-based probe for this enzyme.
Improved facile synthesis of α-amino phosphonates by the reaction of α-amido sulfones with dialkyl trimethyl silyl phosphites catalyzed by Fe(III) chloride
Veeranjaneyulu, Boyapati,Das, Biswanath
, p. 449 - 456 (2017/02/24)
An improved efficient synthesis of α-amino phosphonates has been discovered by the reaction of N-benzyloxycarbonylamino sulfones with dialkyl trimethyl silyl phosphites in the presence of FeCl3as a catalyst. The products were formed in high yie
Mixed alkyl aryl phosphonate esters as quenched fluorescent activity-based probes for serine proteases
Serim, Sevnur,Baer, Philipp,Verhelst, Steven H. L.
, p. 2293 - 2299 (2015/03/04)
Activity-based probes (ABPs) are powerful tools for the analysis of active enzyme species in whole proteomes, cells or animals. Quenched fluorescent ABPs (qABPs) can be applied for real time imaging, allowing the visualization of dynamic enzyme activation
Synthesis of α-aryl-diazophosphonates via palladium-catalyzed cross-coupling of aryl iodides with diethyl diazomethylphosphonate
Kosobokov, Mikhail D.,Titanyuk, Igor D.,Beletskaya, Irina P.
supporting information, p. 6791 - 6794 (2015/01/09)
An efficient procedure for the Pd-catalyzed arylation of diethyl α-diazomethylphosphonate with aryl iodides is described. It can serve as a pathway for the generation of arylated diazophosphonates, which are typically difficult to access. The significance of this methodology was demonstrated via further synthetic transformations of newly synthesized diazo compounds in cyclopropanation, epoxidation, N-H and O-H insertion reactions.
A simple and efficient access to α-amino phosphonates from N-benzyloxycarbonylamino sulfones using indium(III) chloride
Das, Biswanath,Damodar, Kongara,Bhunia, Nisith
experimental part, p. 5607 - 5609 (2009/12/06)
(Chemical Equation Presented) Treatment of N-benzyloxycarbonylamino sulfones with triethyl phosphite catalyzed by InCl3 produces the corresponding protected α-amino phosphonates in high yields (71-92%).
