Human leukocyte elastase HLE

Irreversible inhibition is probably due to the alkylation of a histidine residue.43 Chymotrypsin is selectively inactivated with no or poor inhibition of human leukocyte elastase (HLE) with a major difference the inactivation of HLE is transient.42,43 The calculated intrinsic reactivity of the coumarin derivatives, using a model of a nucleophilic reaction between the ligand and the methanol-water pair, indicates that the inhibitor potency cannot be explained solely by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack 43 Studies on pyridyl esters of 6-(chloromethyl)-2-oxo-2//-1 -benzopyran-3-carboxylic acid (5 and 6, Fig. 11.5) and related structures having various substituents at the 6-position (7, Fig. 11.5) revealed that compounds 5 and 6 are powerful inhibitors of human leukocyte elastase and a-chymotrypsin thrombin is inhibited in some cases whereas trypsin is not inhibited.21... 

The /3-lactam structure can also react with active-serine hydrolases other than PBPs and /3-lactamases. It has been shown that appropriately substituted cephalosporins (e.g., 5.18) are potent mechanism-based inactivators of human leukocyte elastase (HLE, EC 3.4.21.37), a serine endopeptidase involved in the pathogenesis of pulmonary emphysema and other connective tissue diseases [57-60]. Subsequent work has demonstrated that substituted /3-lactams such as 5.19 or 5.20 are more stable HLE inhibitors and have improved potencies [61-63]. 

Very recently, (3-lactam antibiotics have been shown to offer neuroprotection by increasing glutamate transporters expression via gene activation [15] in addition, the discoveries of new biologically active (3-lactams such as cholesterol acyl transferase inhibitors [16-18], thrombin inhibitors [19], human cytomegalovirus protease inhibitors [20], matrix-metallo protease inhibitors [21], inhibitors of human leukocyte elastase (HLE) [22, 23] and cysteine protease [24, 25], and apoptosis inductors [26, 27] have provided much needed motivation for continuous development of new (3-lactam systems. 

Taylor, J. C., Crawford, I., and Hugli, T. E., Limited degradation of the third component (C3) of human complement by human leukocyte elastase (HLE) Partial characterization of C3 fragments. Biochemistry 16, 3390-3396 (1977). 

CONSENSUS SEQUENCES FOR HUMAN PANCREATIC SECRETORY TRYPSIN INHIBITOR (PSTI) VARIANTS, SELECTED BY PHAGE DISPLAY IN THE pSKAN8 VECTOR, WHICH INHIBIT EITHER BOVINE CHYMOTRYPSIN (CHY) OR HUMAN LEUKOCYTE ELASTASE (HLE) WITH SUBNANOMOLAR K, VALUES (REF. 72 AND P. ROTTGEN AND J. COLLINS, UNPUBLISHED DATA)... 

Human leukocyte elastase (HLE EC 3.4.21.37 also known as human neutrophil elastase, HNE) [1] is a strongly basic glycoprotein which is produced by polymorphonuclear leukocytes (neutrophils) and is released from their azurophilic granules [2]. HLE exists as at least four distinct isozymes, which range in molecular weight from 24 [3] to 30 kDa [4] and appear to differ only in carbohydrate content [5]. Furthermore, human sputum elastase (HSE), which is isolated from purulent sputum as at least five distinct isozymes [6], is both immunologically and catalytically indistinguishable from HLE [7] and is believed to be identical to it. 

Human leukocyte elastase (HLE) is a serine protease which is used in the lung to degrade necrotic tissue and invading bacteria. Under normal conditions, the activity of elastase is controlled by several endogenous inhibitors such as al-protease-inhibitor. If the balance between protease and inhibitor is shifted, then elastase also attacks healthy tissue, leading to emphysema. 

The isothiazol-3(2//)-one 1,1-dioxides 254-257 with stabilizing aryl substituents in the 2-, 4- and/or 5-position are potential inhibitors toward human leukocyte elastase (HLE) (03ZN(B)111, 05JEIMC341). HLE is a serine protease implicated in several inflammatory diseases and represents a major target for the development of low-molecular weight inhibitors. 

Human leukocyte elastase (HLE) is a serine protease produced and stored by PMNL and involved in the tissue destruction observed in many inflammatory diseases such as chronic arthritis. In fact, administration of exogenous elastase inhibitors could be a means of protecting tissues from proteolytic attack. 

Human leukocyte elastase (HLE) is a serine proteinase involved in inflammation and tissue degradation. It is... 

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