The Natural Polypeptides as Significant Elastase Inhibitors

Abstract

Human neutrophil elastase (HNE) is a major cause of the destruction of tissues in cases of several different chronic andinflammatory diseases. Overexpression of the elastase enzyme plays a significant role in the pathogenesis of various diseases including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome, rheumatoid arthritis, the rare disease cyclic hematopoiesis (or cyclic neutropenia), infections, sepsis, cystic fibrosis, myocardial ischemia/reperfusion injury and asthma, inflammation, and atherosclerosis. Human neutrophil elastase is secreted by human neutrophils due to different stimuli. Medicine-based inhibition of the over-activation of neutrophils or production and activity of elastase have been suggested to mend inflammatory diseases. Although the development of new elastase inhibitors is an essential strategy for treating the different inflammatory diseases, it has been a challenge to specifically target the activity of elastase because of its overlapping functions with those of other serine proteases. This review article highlights the reported natural polypeptides as potential inhibitors of elastase enzyme. The mechanism of action, structural features, and activity of the polypeptides have also been correlated wherever they were available.

Peptide Human Neutrophil Elastase Inhibitors from Natural Sources: An Overview

“…Indeed, the subsites S1 to S4 of the e cupied by the 2-amino-2-butenoic acid (Abu) and the N-terminal amino aci is similar to Tutuilamide B, except for the lack of an alanine residue and t an additional methylene in the side chain (Figure 5). Tutuilamides A-C ha for the inhibition activity against serine proteases, e.g., porcine pancreatic Tutuilamides A and B are the most active as inhibitors against PPE, with an Different peptides are produced by marine cyanobacteria belonging to genus Lyngbya [23]. Lyngbya confervoides coming from the Florida Atlantic coast is a producer of lyngbyastatin 4, a depsipeptide showing two peculiar residues of homotyrosine and Ahp; it has the ability to inhibit human neutrophil elastase, with an IC 50 value of 49 nM.…”

“…Eight cyclodepsipeptides have been produced by the filamentous fungi Beauveria felina after the addition of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, to the culture medium; three of them are new compounds, e.g., desmethylisaridin C2, desmethylisaridin E and isaridin F [ 22 ]. This is an example of an epigenetic tool used for obtaining inhibitor peptides from fungal sources [ 23 ]. Among them, Desmethylisaridin C2, isaridin E, isaridin C2 and roseocardin ( Figure 3 ) are able to inhibit elastase release induced by formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) in human neutrophils and to express an anti-inflammatory action without toxicity for human neutrophils.…”

“…Different peptides are produced by marine cyanobacteria belonging to genus Lyngbya [ 23 ]. Lyngbya confervoides coming from the Florida Atlantic coast is a producer of lyngbyastatin 4, a depsipeptide showing two peculiar residues of homotyrosine and Ahp; it has the ability to inhibit human neutrophil elastase, with an IC 50 value of 49 nM.…”

Sequence preference and scaffolding requirement for the inhibition of human neutrophil elastase by ecotin peptide

“…8 Indeed, it has been shown that peptides derived from natural protein inhibitors are preferred over synthetic peptides as they cause less cytotoxicity. 9 Current natural inhibitor peptides, however, are unstable under pathophysiological conditions, show a lack of precise selectivity, and have an ineffective inhibitory potential. 2 Synthetic peptides with modified amino acids are therefore frequently sought and optimized to improve the affinity and inhibitory potential of peptides toward proteases.…”

Single crystal, Hirshfeld surface, DFT analyses of (E)‐2‐(2‐chloro‐6‐fluorobenzylidene)hydrazinecarbothioamide: Elastase inhibition and DNA binding studies

“…Upregulation of the enzyme elastase assumes a huge part in the pathogenesis of different sicknesses including persistent obstructive pneumonic illness (COPD), intense respiratory pain condition, rheumatoid joint inflammation, the uncommon infection cyclic hematopoiesis (or cyclic neutropenia), sepsis, contaminations, cystic fibrosis, ischemia/reperfusion myocardial asthma, injury and irritation, and atherosclerosis [ 15 ] ; hence, study on drug or drug like molecules is important to explore a compound as potential candidate for its potency towards elastase inhibition or on the other hand for the disclosure of a chemical for treatments of different inflammatory diseases.…”