Human neutrophilic elastase

HNE Human neutrophil elastase HNG Human neutrophil gclatinase (MMP-9)... 

The family Droseraceae consists of four genera and about 100 species of perennial herbs, of which Drosera burmannii Vahl, Drosera rotundifolia L, Drosera indica L., and Drosera peltata Sm. are used in Asia for the treatment of cough. Naphthoquinones and flavonoids, which occur in this family, have not been fully studied for pharmacology, and it appears that flavonoids inhibit human neutrophil elastase, hence the potential for the treatment of inflammation. 

To avoid the problems with kinetic control of a reaction during peptide bond formation, it is recommended that longer peptide phosphonates be synthesized stepwise by extension in the N-terminal direction, starting with diphenyl l-(aminoalkyl)phosphonates. The longer coupling time will provide peptide products that are usually an equivalent (or close to equivalent) mixture of diastereomers. The synthesis of longer peptides is demonstrated by the synthesis of Boc-Val-Pro-Valp(OPh)2, which is an excellent inhibitor of human neutrophil elastase (kobs/[I] = 27,000 M 1s 1)J38 ... 

We have extended these studies to five /V-bcnzoylazolcs (imidazole, pyrazole, indole, benzimidazole and carbazole) [35] but this time centered on crystallography and solid state NMR. 9-Benzoylcarbazole (29) has a low barrier (29.7 kJ mol1) and shows spontaneous resolution (both axial enantiomers were separated by crystallization). Recently, /V-benzoylpyrazoles have been described as inhibitors of human neutrophil elastase [36],... 

Diazetidin-2,4-dione has been found to be a chymase inhibitor (IC50 4.0nM). It has been found that 1,3-diazetidin-2,4-dione derivatives possess high activities against bovine pancreatic cr-chrymotrypsin, human cathepsin G, and human neutrophil elastase. Some of the derivatives of l,3-diazetidin-2,4-diones have been shown to be effective as a scaffold for serine protease inhibitors <2001BML1691>. Further, 1,3-diazetidinone containing scaffolds have been found to possess potential antibacterial properties (Section 2.13.7.3). 

Human neutrophil elastase (HNE) is a serine containing enzyme which is one of the most destructive of proteolytic enzymes, being able to catalyze the hydrolysis of the components of connective tissue. It has been implicated in the development of diseases such as emphysema, cystic fibrosis, and rheumatoid arthrisis. /3-Sultams are excellent candidates for exploring the mechanism of sulfonation and possible inhibition of serine protease enzymes. A-Benzoyl... 

Human neutrophil elastase is the proteinase that has received by for the most attention over the last 30 years primarily due to the foci that it was thought to be the rntyor factor involved in the development of emphysema. This assumption was derived from the observation of Eriksson In 1963 that individuals with an inherited deficiency of cti-PI developed emphysema at an early age [11]. One year later. Gross showed that emphysema could be produced in experimental animals after intratracheal administration of papain, a plant proteinase with a... 

S. Sinha, W, Wdouk, S. Karr, I. Giles, W. Bode, and J. Travis. Primary structure of human neutrophil elastase, Proc. Natl Acad. Set. M222S (1987),... 

H. Takahashi,T. Nnkiwa, K. Yoihhnum, G. D. Quick. D. J. States, 3. Whang-PeoR. T. Knrnsen, and R. O. Crystal. Structure of the human neutrophil elastase gene. J.BioL Chem 263 14739 (1988). 

D. Parley, J. Travis, and G. Salvesen. Die human neutrophil elastase gene. Aialysfe of the nucleotide sequence reveals three distinct classes of repetitive DNA. BioL Chem Hoppe-Styier 57t 737 (1989). 

E. C. Luccy, P. J. Stone. D. EL Ciccolclla, R. Bcuer, T. 0. Christensen, R. C. Thompson, and G- L. Snider. Recombinant human secretory leukocyte-protease inhibitor in vitro properties, and amelioration of human neutrophil elastase-induced emphysema and secretory cell metaplasia in the hamster. /. Lab. Clin. hied. 7/5 224... 

E. C. Lucey, P. J. Stone T. O. Christensen, R. Bieuer, J. D. Calcic, and G. L Snider. Effect of varying the time interval between intratracheal administration of egliiM and human neutrophil elastase an prevention of emphysema and secretory cell metaplasia... 

C. P. Dom, and K, HoogSteen. Structure of human neutrophil elastase in complex with a peptide diloramethyl ketone inhibitor at 134 A resolution. Proc. NatL Sci. USA 86 7 (im). 

Charlton J, Sennello J, Smith D, In vivo imaging using an aptamer inhibitor of human neutrophil elastase, Chem. Biol., 4 809-816, 1997. 

Gleeson MP, IH Hillier, NA Burton (2004) Theoretical analysis of peptidyl alpha-ketoheterocyclic inhibitors of human neutrophil elastase Insight into the mechanism of inhibition and the application of QM/MM calculations in structure-based drug design. Organic Biomolecular Chemistry 2 (16) 2275-2280... 

Utility Human Neutrophil Elastase Inhibitor in the Treatment of... 

Edwards PD, Zottola MA, Davis M et al (1995) Peptidyl alpha-ketoheterocyclic inhibitors of human neutrophil elastase. In vitro and in vivo potency of a series of peptidyl alpha-ketobenzoxazoles. J Med Chem 38 3972-3982... 

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. 

Meyer KC, Lewandoski JR, Zimmerman JJ, Nunley D, Calhoun WJ, Dopico GA Human neutrophil elastase and elastase/alpha 1-antiprotease complex in cystic fibrosis. Am J Respir Dis 144 (1991) 580-5. 

Amatini, R., Wilson, R., Rutman, A., Read, R., Ward, C., Burnett, D., Stockley, R.A. and Cole, P.J. (1991). Efiects of human neutrophil elastase and Pseudomonas am pnosa pro-teinases on human respiratory epithelium. Am. J. Respir. Cell Mol. Biol. 4, 26-32. 

Angelastro, M. R., Baugh, L. E., Bey, P., et al. (1994) Inhibition of human neutrophil elastase with peptidyl electrophilic ketones. 2. Orally active PG-Val-Pro-Val pentafluoroethyl ketones. J. Med. Chem., 37, 4538 1553. 

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