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Proteolytic enzymes

About: Proteolytic enzymes is a research topic. Over the lifetime, 23096 publications have been published within this topic receiving 835544 citations.


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Journal ArticleDOI
01 May 1983-Nature
TL;DR: New highly potent (IC50 = 10−9−10−8 M) competitive inhibitors of renin are reported in which statine, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of the pig renin substrate.
Abstract: The proteolytic enzyme renin (EC3.4.99.19) cleaves the protein substrate angiotensinogen to yield angiotensin I, the decapeptide substrate transformed by converting enzyme into the pressor substance angiotensin II1. Although the contribution of this pathway to the maintenance of normal blood pressure is unclear, it seems to be a major factor in various hypertensive states2–4. Important progress in the control of hypertension has been achieved by development of the potent inhibitors SQ-14,225 (captopril)5,6 and MK-421 (enalapril maleate)7–9 which block the generation of angiotensin II by the inhibition of angiotensin converting enzyme. An attractive alternative to the inhibition of converting enzyme would be the blockade of the preceding step in the cascade, the renin reaction. We report here new highly potent (IC50 = 10−9−10−8 M) competitive inhibitors of renin in which statine, (3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of the pig renin substrate (Fig. 1).

165 citations

Journal ArticleDOI
TL;DR: There is strong evidence that the effects of tryptic digestion result exclusively from perturbations of superficial structures of the cell membrane, and there is no evidence that this specific and well characterized effect oftryptic digestion is subject to facile and spontaneous repair.

165 citations

Journal ArticleDOI
01 Mar 1974-Diabetes
TL;DR: There was considerable species variation in insulin binding, with the placental membranes of the guinea pig and monkey having the highest and those of the rat having the lowest binding.
Abstract: The existence of polypeptide hormone receptors in the human placenta was evaluated by studying the specific binding of 125-I-labeled insulin, human growth hormone (hGH), human pro lac tin (hPRL) and glucagon to a defined placental membrane fraction. Only insulin showed specific binding to placental membranes. The binding of 125-I-insulin was time and temperature dependent. Its dissociation from the membrane was first order with a half time, at 24° C, of twenty minutes. Specific binding was readily observed at a concentration of 5 × 10−11 (7.5 μU./ml.). Inhibition of 125-I-insulin binding by unlabeled insulin was 30 per cent at 10−9 M, and >90 per cent at 10−9 M. Desalanine insulin was equally effective in inhibiting the binding of 125-I-insulin. Proinsulin was about twenty times less effective, and desoctapeptide insulin was even less effective. Structurally unrelated polypeptide hormones were without significant inhibitory effect. Binding sites of relatively high affinity (K1 = 4.2 × 108 M−1) and low capacity could be distinguished from those of lower affinity (K2 = 0.7 × 108M−1) and higher capacity. Insulin degrading activity was shown to be present in the placental membranes. Under standard binding assay conditions, less than 20 per cent of the 125-I-insulin present was degraded. The 125-I-insulin could be eluted from the membranes and appeared intact by several criteria. Specific binding was augmented by Ca++ and other divalent cations but was unaffected by high sodium chloride concentrations. Binding was greatly reduced by pretreatment of membranes with proteolytic enzymes. Incubation with phospholipase C, RNase and neur-aminidase had relatively little effect on binding. Insulin binding was unaffected by maternal diabetes but was reduced in membranes from early gestational placentas. There was considerable species variation in insulin binding, with the placental membranes of the guinea pig and monkey having the highest and those of the rat having the lowest binding. The characteristics of the insulin binding sites in the human placenta are similar to those in established insulin target tissues.

165 citations

Journal ArticleDOI
TL;DR: The purpose of this article is to provide an overview of the current knowledge of genome structure and gene expression in the enteric caliciviruses.
Abstract: The application of molecular techniques to the characterization of caliciviruses has resulted in an extensive database of sequence information. This information has led to the identification of 4 distinct genera. The human enteric caliciviruses have been assigned to 2 of these genera. This division is reflected not only in sequence diversity but in a fundamental difference in genome organization. Complete genome sequences are now available for 5 enteric caliciviruses and demonstrate that human and animal enteric caliciviruses are phylogenetically closely related. Currently, there is no cell culture system for the human viruses; therefore, studies have relied on heterologous expression and in vitro systems. These studies have shown that in both human and animal viruses the viral nonstructural proteins are produced from a polyprotein precursor that is cleaved by a single viral protease. The purpose of this article is to provide an overview of the current knowledge of genome structure and gene expression in the enteric caliciviruses.

165 citations

Journal ArticleDOI
TL;DR: Preparations of bovine pancreatic deoxyribonuclease obtained by the ammonium sulfate precipitation procedure of Kunitz can be further purified by chromatography on sulfoethyl-Sephadex at pH 4.70 and show that the enzyme contains glucosamine and mannose and establish DNase as a glycoprotein.

165 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202350
2022113
2021358
2020434
2019358
2018472