Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of dipeptides which contained phosphonate analogs of proline and piperidine-2-carboxylic acid (homoproline) have been synthesized and tested as inhibitors of DPP-IV. The rates of inhibition of DPP-IV by these compounds are moderate, but the inhibitors are quite specific. The best inhibitor in the series is Ala-PipP(OPh-4-Cl)2 (13), which has a k(inact) of 0.353 s-1 and KI of 236 microM. The DPP-IV inhibitors Ala-ProP(OPh)2 (6), Ala-ProP(OPh-4-Cl)2 (12), and Ala-PipP(OPh-4-Cl)2 (13) do not inhibit trypsin, human leukocyte elastase (HLE), porcine pancreatic elastase (PPE), acetylcholinesterase, papain, and cathepsin B. However, compounds 12 and 13 inhibited chymotrypsin slowly. Most of these dipeptides containing a homoproline phosphonate residue (PipP) or a Pro phosphonate residue (ProP) at the P1 site are stable in a pH 7.8 buffer with half-lives of several hours to several days. DPP-IV inhibited by 6, 7 (Ala-PipP(OPh)2), 12, or 13 is quite stable, and no enzyme activity was recovered after removal of excess inhibitor and incubation in buffer for 1 day. Since the phosphonate inhibitors are specific toward DPP-IV and the inhibited enzymes are stable, they should be useful in establishing the biological functions of DPP-IV and may be useful therapeutically in the prevention of the rejection of transplanted tissue.
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PMID:Dipeptide phosphonates as inhibitors of dipeptidyl peptidase IV. 796 57

Tegumental extracts from adult worms of Schistosoma mansoni contain an inhibitory activity to the S. mansoni 28-kDa serine protease and to pancreatic elastase. By using biotinylated elastase and streptavidin-agarose, the postulated protease inhibitor has been isolated from the crude worm extract in a single step. Monospecific rabbit antibodies raised against the protease inhibitor have immunoprecipitated a 56-kDa [35S]Met-labeled serine protease inhibitor which was designated Smpi56 (S. mansoni protease inhibitor, 56 kDa). Smpi56 binds tightly to and inhibits the 28-kDa protease of S. mansoni and pancreatic and neutrophil elastase but not papain, pepsin, thrombin, trypsin, chymotrypsin, proteinase K, urokinase and acetylcholinesterase. The biological function of Smpi56 is still not known, but in view of its elastase inhibitory activity it may be speculated that the parasite is employing Smpi56 to protect itself from activated neutrophils. Smpi56 may also potentially protect the parasite from its endogenous 28-kDa protease.
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PMID:Schistosoma mansoni: isolation and characterization of Smpi56, a novel serine protease inhibitor. 811 69

Carbamyl sulfonate (CS) compounds are a novel class of carbamates derived from amino acid methyl esters. They have the general structure RCH(COOCH3)NH(CO)SO-3K+, where R is the sidechain of the parent amino acid. These compounds were developed as active site-directed inhibitors of human leukocyte elastase (HLE). The purpose of this study was to characterize the inhibition of hen brain neurotoxic esterase (neuropathy target esterase, NTE), horse serum butyrylcholinesterase (BuChE), and bovine erythrocyte acetylcholinesterase (AChE) by CS analogs derived from the methyl esters of L-ala, D-norval, L-norval, L-phe, L-val, L-norleu, D-met, and L-met. Bimolecular rate constants of inhibition (ki) for NTE ranged from 0.571 for L-ala-CS to 17.7 mM-1 min-1 for L-norleu-CS (10-min I50 values of 123 and 3.92 microM, respectively). Potency against NTE increased with chain length for straight-chain R-groups of L-CS compounds. Unlike HLE, NTE was only weakly stereoselective for CS compound enantiomers. The L-isomers were weaker inhibitors of BuChE than NTE (10-min I50 range of 742 to 35.6 microM). In contrast to the L-enantiomers, the I50 plots of D-met-CS and D-norval-CS were not linear for BuChE, suggesting a possible stereospecific mechanistic shift for inhibition of this enzyme, AChE was not effectively inhibited by any of the CS compounds (I50 values > 750 microM). The specificity and charged nature of CS compounds give these unusual NTE inhibitors potential advantages for mechanistic studies of organophosphorus compound-induced delayed neurotoxicity (OPIDN) and its protection or potentiation.
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PMID:Inhibition of neurotoxic esterase in vitro by novel carbamates. 907 5

The synthesis of a series of new isothiazol-3(2H)-one 1,1-dioxides with halogenated (mostly fluorinated) pyridinyl and pentafluorophenyl substituents at 2-position is reported. These compounds (18-24) became easily accessible from 2-thiocyanato-1-carboxaldehydes and aminopyridines, pentafluoroaniline, respectively, by an isothiazolium cyclization-oxidation route. Compound 21 exhibited an IC(50) value of 3.1 microM toward human leukocyte elastase. The proteases cathepsin G, trypsin, cathepsin L, and angiotensin-converting enzyme, and the serine esterases acetylcholinesterase and cholesterol esterase were not inhibited by 21.
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PMID:Synthesis and elastase-inhibiting activity of 2-pyridinyl-isothiazol-3(2H)-one 1,1-dioxides. 1870

The fungus Phaeosphaeria spartinae is an endophyte of the marine alga Ceramium sp. Investigation of this marine-derived fungus led to the isolation of spartinoxide (1), which is the enantiomer of the known compound A82775C (2). Additionally, the known metabolites 4-hydroxy-3-prenyl-benzoic acid (4) and anofinic acid (5) were obtained. The structures of all compounds were established from extensive spectroscopic investigations. Compounds 1, 4 and 5 were assayed against the enzymes human leukocyte elastase (HLE), trypsin, acetylcholinesterase and cholesterolesterase. Compounds 1 and 4 showed potent inhibition of HLE with IC50 values of 1.71 +/- 0.30 microg/mL (6.5 microM) and 1.67 +/- 0.32 microg/mL (8.1 microM), respectively.
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PMID:Spartinoxide, a new enantiomer of A82775C with inhibitory activity toward HLE from the marine-derived Fungus Phaeosphaeria spartinae. 2073 43