Aminopeptidase inhibitors

Ubenimex, [(2(3),3(R))-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, was isolated as an inhibitor of aminopeptidases, on which it acts as a strong, reversible transition-state analogue inhibitor (293). Analogues of ubenimex have been made and some other aminopeptidase inhibitors, not all of them peptides, have been isolated from streptomycetes (294—296). 

A recent study, however, has shown that aminopeptidase activity is present on the surface of porcine buccal mucosa, and that various aminopeptidase inhibitors, including amastatin and sodium deoxycholate, reduce the mucosal surface degradation of the aminopeptidase substrate, leucine-enkephalin [149], Since the peptidases are present on the surface of the buccal mucosa, they may act as a significant barrier to the permeability of compounds which are substrates for the enzyme. In addition to proteolytic enzymes, there exist some esterases, oxidases, and reductases originating from buccal epithelial cells, as well as phosphatases and carbohydrases present in saliva [154], all of which may potentially be involved in the metabolism of topically applied compounds. 

Hussain MA, Koval CA, Shenvi AB, Aungst BJ (1990) Recovery of rat nasal mucosa from the effects of aminopeptidase inhibitors. J Pharm Sci 79 398-400. 

De, A. Basak, P. Iqbal, J. Polyaniline Supported Cobalt Catalyzed One Pot Stereoselective Synthesis of the Structural Analogs of Aminopeptidase Inhibitor Bestatin, Tetrahedron Lett. 1997, 38, 8383. 

Ishida K, Matsuda H, Murakami M, Yamaguchi K (1997) Microginins 299-A and -B, Leucine Aminopeptidase Inhibitors from the Cyanobacterium Microcystis aeruginosa (NIES-299). Tetrahedron 53 10281... 

Enzyme inhibitors can reduce the metabolic barrier to nasal delivery. The selection of an inhibitor is made on the basis of its ability to inhibit effectively the enzyme primarily responsible for the degradation of a particular compound. The coadministration of peptidase and protease inhibitors such as bacitracin, bestatin, amastatin, and aminoboronic acid derivatives has been found to promote the absorption of LHRH and growth hormone [42,43]. Aminopeptidase inhibitors in particular are effective in improving the bioavailability of enkephalins [44]. 

Grembecka J, Sokalski WA, Kedzierski P (2000) Computer-aided design and activity prediction of leucitine aminopeptidase inhibitors. J Comput Aided Mol Des 14 531-544... 

Aminopeptidase inhibitor also described as a metalloproteinase inhibitor. 

Diprosone betamethasone. diprOtin A is a tripeptide that is an ENZYME INHIBITOR with selectivity as an aminopeptidase inhibitor active against dipeptidylpeptidase IV (EC 3.4.11). It can be used as a pharmacological tool in experimental analytical studies, dipyridamole [ban, inn, usan] (Persantin ) is a pyrimidine derivative, a coronary VASODILATOR, a (class la) ANTIARRHYTHMIC, an adenosine UPTAKE INHIBITOR causing indirect adenosine receptor activation, and enhances effects of anticoagulants and is a platelet AGGREGATION INHIBITOR. 

Other classes include aldehyde dehydrogenase inhibitors aldose reductase inhibitors aminopeptidase inhibitors aromatase inhibitors carboxypeptidase inhibitors cyclooxygenase inhibitors dihydrofolate... 

There have been attempts to develop analgesic agents that work indirectly, through interfering with the breakdown of natural opioids in the body. Experimentally, some peptidase inhibitors have been shown to have analgesic actions mainly a combination of thiorphan (an inhibitor of NEP ( enkephalinase ) and bestatin (an inhibitor of aminopeptidase B see aminopeptidase inhibitors NEUTRAL... 

Other members of the metalloprotease family cleave oligopeptides (arbitrarily defined as having less than 50 amino acid residues) and do not necessarily act on proteins. These include a number of neuropeptidases of special interest and a number are discussed elsewhere. See ACE inhibitors aminopeptidase inhibitors carboxypeptidase inhibitors endopeptidase inhibitors neutral endopeptidase inhibitors. 

Peptidases. Others members of the serine protease family, cleave oligopeptides and do not necessarily act on proteins. These include two peptidases of particular interest (dipeptidylpeptidase IV and proline endopeptidase). See also AMINOPEPTIDASE INHIBITORS CARBOXYPEPTIDASE INHIBITORS ... 

Protease Inhibitors - Bestatin (56.), an aminopeptidase inhibitor isolated from Streptomyces olivoreticuli has been reported to stimulate cellular and humoral immunity against sheep red blood cells in micel53. Blastogenesis of peripheral lymphocytes from guinea pigs by concanavalin A and PHA was enhanced. 15, 155 Moreover, bestatin appeared to increase the effects of bleo-... 

The potent enzyme (aminopeptidase) inhibitor bestatin 161 provides another perfect bridge between the amino- and the hydroxy-acids. At first sight bestatin appears to be a dipeptide but only one of the components, leucine 163 is a normal a-amino acid. The other half 162 is a P-amino acid and also an a-hydroxyacid and that might give us the idea that malic acid 34, with the same absolute configuration at the secondary alcohol, could provide a chiral pool starting material. 

Preparation of novel specific aminopeptidase inhibitors with a cyclic imide skeleton 00YZ909. 

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