Novel diphenyl esters of peptidyl α-aminoalkylphosphonates as inhibitors of chymotrypsin and subtilisin

Development and binding characteristics of phosphonate inhibitors of SplA protease from Staphylococcus aureus

“…Our investigation of the influence of structurally diverse substitutions on the phenyl ester rings indicated that inclusion of electron‐withdrawing moieties increases the level of inhibition of SplA, as was previously reported for other proteases …”

“…All final compounds were purified using column chromatography on silica gel. Other examined phosphonate inhibitors were synthesized as described previously: 1 , 2–4 , 5–6 , 7 , 8–9 , 10–16 , 17–18 , 20–22 , 29–34 , and 41 …”

“…Our investigation of the influence of structurally diverse substitutions on the phenyl ester rings indicated that inclusion of electron-withdrawing moieties increases the level of inhibition of SplA, as was previously reported for other proteases. 15,20 Studies on phosphonate and other transitionstate-analog inhibitors, such as boronic acid derivatives and aldehydes, have demonstrated that inclusion of the sequences of efficient substrates in the peptidyl moieties of inhibitors generally increases inhibitor potency and selectivity. 13 Accordingly, we report here that extension of the peptide moiety increases potency against SplA compared with single amino acid derivatives.…”

A Layered Zinc(II) Coordination Polymer Containing Infinite Zn–S–Zn Chains and its Cluster‐like Derivative

“…Previously we reported the synthesis and application of a highly efficient probe for the detection of CatG in human peripheral blood mononuclear cells (PBMCs) to study its role in the invariant chain processing pathway of primary human B‐cells as well as proinsulin processing 5. The introduction of a particular group within the aromatic ester structure greatly improved (or almost completely abolished) the inhibitory activity of aminophosphonates 21–23. Alterations within the ester ring structure improved the selectivity of a particular derivative, thereby making it feasible to distinguish between two serine peptidases with a similar substrate‐recognition pattern.…”

Discovery of non-competitive thrombin inhibitor derived from competitive tryptase inhibitor skeleton: Shift in molecular recognition resulted from skeletal conversion of carboxylate into phosphonate

“…10 In addition, several research groups have shown that peptidyl diphenyl phosphonate derivatives exhibit inhibitory activity against various trypsin-like serine proteases. [11][12][13][14][15] Meanwhile, since the end of the 20th century, we have been engaged in developing sphingomyelinase (SMase) inhibitors based on the replacement of the phosphodiester moiety of sphingomyelin with isosteric difluoromethylenephosphonic acid. Using this strategy, we have successfully developed phosphonatecontaining inhibitors against lysosomal acid sphingomyelinase (A-SMase) and membrane-bound neutral sphingomyelinase (N-SMase).…”