Effect Of Synthetic Protease Inhibitor Research Articles

Efeito de inibidores de proteases na atividade enzimática de Coccus viridis em Coffea arabica

A cultura do café no Brasil tem muita importância econômica e relevância no setor social. É possível que as injurias causadas pelo inseto Coccus viridis (cochonilha-verde) seja um dos motivos da redução de sua produtividade. As plantas, ao serem injuriadas, são capazes de aumentar a síntese de inibidores de proteases (IPs) por toda sua extensão. Estudos demonstraram que insetos alimentados com plantas previamente pulverizadas com inibidores sintéticos têm seu desenvolvimento afetado. Assim, este trabalho teve por objetivo avaliar os efeitos dos inibidores de proteases sintéticos, benzamidina e berenil, sobre a atividade proteolítica intestinal de C. viridis. Plantas de Coffea arabica foram infestadas com ninfas de C. viridis e pulverizadas com benzamidina e berenil, em quatro diferentes concentrações: 0; 0,25%; 0,5% e 0,75% (p/v). A resposta bioquímica do inseto foi avaliada após 24 horas da pulverização, coletando-se os insetos. A atividade das serino-proteases tripsina-like (amidásica e esterásica) e quimotripsina-like esterásica foi reduzida pela presença dos inibidores. O mesmo se obteve em relação à atividade das cisteíno-proteases.

Serine and Cysteine Proteases in Sulfur Mustard-Exposed Hairless Mouse Skin: Enzymatic Activity and Inhibition Profiles

AbstractInflammatory reactions associated with sulfur mustard (bis(2-chloroethyl)sulfide, SM)-induced skin pathology, including the release of potent proteolytic enzymes capable of destroying cutaneous connective tissue proteins, are not well defined in vivo. In this study, protease activities were measured as potential indicators of SM-induced skin injury in a hairless mouse sulfur mustard vapor exposure model. We also investigated the effects of synthetic protease inhibitors on SM-induced proteolytic activity. Skin homogenates prepared from hairless mouse dorsal skin exposed to SM vapor (1.4 g/m3) were assayed for serine and cysteine protease activities using synthetic chromogenic and fluorogenic substrates. Skin samples were obtained 24 h after SM challenge from animals exposed for either 6 or 12 min, while controls were obtained from unexposed skin. With 6 min SM-exposed skin, significantly higher elastase, tryptase, cathepsin B, cathepsin L, and calpain II enzymatic activities were detected compared ...

Effect of synthetic protease inhibitor on histologic changes and free radical activity in hamsters with pancreatic cancer.

To investigate the effects of synthetic trypsin inhibitors on pancreatic cancer, camostat (FOY-305) was administered orally to hamsters with experimental pancreatic cancer induced by diisopropanol nitrosamine (DIPN). The effect of free radicals on carcinogenesis was examined by measuring the tissue levels of the scavengers superoxide dismutase (SOD) and glutathione peroxidase (GSX-Px), and pancreatic tissues were examined histologically. Cancers developed in all hamsters that survived 24 weeks in the DIPN group and the FOY group, but 80% of the cancers in the DIPN group were tubular adenocarcinomas, and 91% of those in the FOY group papillary adenocarcinomas. The SOD activity in the DIPN group was significantly lower in the cancerous area and the borderline region than in the non-cancerous region and normal tissue. SOD activity in the cancerous and borderline regions was higher in the FOY groups than in the DIPN group. GSH-Px levels in the borderline and non-cancerous regions were significantly higher in the FOY group than in the DIPN group. These results suggest that the synthetic protease inhibitor slows the progress of pancreatic cancer by its free radical scavenging activity.

Effect of synthetic protease inhibitor on the sphincter of Oddi function in dogs

Effect of synthetic protease inhibitor on the sphincter of Oddi function in dogs

The effects of synthetic protease inhibitors on human proinsulin production by recombinantBacillus subtilis strain

Two inexpensive inhibitors non-toxic to B. subtilis cells, O,O-diethyl-1-(N-α-hydrohexafluoro-isobutyryl)amino-1-methyl-propylphosphonate and O,O-diisobutyl-1-[2-(ethoxycarbonyl)amino-perfluoroprop-2-yl]-1-methylpropylphosphonate, when added to the culture broth, are able to prevent the proteolytic degradation of recombinant human proinsulin, secreted byB. subtilis AJ73apr73 npr− cells.

細胞接着蛋白に対するａｍｉｄｉｎｏｎａｐｈｔｏｌ誘導体の抑制作用

We have recently reported that nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, inhibited the binding of fibrinogen to ADP-stimulated human platelets in an antagonistic manner. In respect to the similar effect of FUT-175 to ArgGly-Asp-Ser (RGDS), synthetic peptide constituted cell attachment domain of fibronectin, on fibrinogen binding to stimulated platelets, we have examined the effects of synthetic protease inhibitors on both fibronectin binding to thrombin-stimulated platetets and fibronectin-mediated cell attachment.To exclude the direct inhibitory effect of the agents against thrombin, paraformaldehyde-fixed thrombin-stimulated platelets which expressed fibronectin-binding sites were used in this study. Among the synthetic inhibitors examined, FUT-175 and FUT-5923 which have amidinonaptol in their structure as active inhibitory sites, blocked the binding of 125I-fibronectin to thrombin-stimulated platelets dose-dependently. 125I-fibrinogen binding to ADP-stimulated fixed platelets was also inhibited by both FUT-175 and FUT-5923. These data indicated that the inhibition of amidinonaphtol derivatives was not via blockade of binding site expression.Attachment of normal rat kidney fibroblasts to fibronectin-coated plate was inhibited by these amidinonaphtol derivatives, dose dependently. The agents were also affected fibronectin dependent cellular spreading.These results suggest that the inhibitory effects of amidinonaphtol derivatives on the cellular interaction with these adhesive proteins might be related to conformational characteristics, not to their inhibitory activities against proteases.

Proteoglycan degradation by a chondrocyte metalloprotease: Effects of synthetic protease inhibitors

Synthetic inhibitors of a chondrocyte metalloprotease (CMP) were assessed for potency. Proteoglycan core protein was used as substrate. The ic 50 values were between 2 × 10 −6 and 7 × 10 −6 M for two types of inhibitors, thiol tripeptides and N-carboxyalkyl peptides. Hydroxamic acid peptides were more potent, with ic 50 values of 3.2 × 10 −8 to 6.0 × 10 −8M. These results confirm inhibitory concentrations reported using a proteoglycan-polyacrylamide bead assay. The slopes of the doseresponse curves for the thiol compounds were steeper than the slopes for the other two types of compounds. All of the culture media tested inhibited CMP to some extent. Some media also interfered with inhibitor activity. In Ham's F10 nutrient medium, minimum CMP inhibition occurred, and all four hydroxamic acid peptides retained their activity for 1–2 days at 37°. One thiol peptide compound assayed lost activity in 1 hr in thiocyanate-treated serum. All four hydroxamic acid peptides assayed retained activity in thiocyanate-treated serum after 3 days at 37°. The hydroxamic acid peptides may provide a way to block endogenous CMP activity in vivo and to assess the role of CMP in normal and experimentally altered cartilage. They are more potent than other known CMP inhibitors. They retain activity in culture media and serum conditions used for in vivo and in vitro tests of CMP activity and toxicity.

Effect of the Synthetic Protease Inhibitor [<italic>N,N</italic>-Dimethylcarbamoyl-methyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate on Carcinogenesis by 3-Methylcholanthrene in Mouse Skin<xref ref-type="fn" rid="FN2">2</xref>

The effect of the potent synthetic protease inhibitor [N,N-dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)-phenylacetate] methanesulfate (FOY-305) on skin carcinogenesis in ddY mice was examined over a total observation period of 105 days. Administration of 0.1% FOY-305 in the diet suppressed the incidence of carcinomas induced by repeated local application of the carcinogen 3-methylcholanthrene (MCA) (P less than .05) in mouse skin and delayed the time of appearance of the skin tumors (P less than .001). There was no significant difference in the number of tumors per tumor-bearing mouse and the size of the tumors between mice treated with MCA and mice treated with MCA plus FOY-305.