title: Tailoring elastase inhibition with synthetic peptides.
abstract: Chronic wounds are the result of excessive amounts of tissue destructive proteases such as human neutrophil elastase (HNE). The high levels of this enzyme found on those types of wounds inactivate the endogenous inhibitor barrier thus, the search for new HNE inhibitors is required. This work presents two new HNE inhibitor peptides, which were synthesized based on the reactive-site loop of the Bowman-Birk inhibitor protein. The results obtained indicated that these new peptides are competitive inhibitors for HNE and, the inhibitory activity can be modulated by modifications introduced at the N- and C-terminal of the peptides. Furthermore, these peptides were also able to inhibit elastase from a human wound exudate while showing no cytotoxicity against human skin fibroblasts in vitro, greatly supporting their potential application in chronic wound treatment.
authors.affiliation: Universidade do Minho, Departamento de Engenharia Têxtil, Campus de Azurém, 4800-058, Guimarães, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Vasconcelos
authors.forename: Nuno G
authors.initials: NG
authors.lastname: Azoia
authors.forename: Ana C
authors.initials: AC
authors.lastname: Carvalho
authors.forename: Andreia C
authors.initials: AC
authors.lastname: Gomes
authors.forename: Georg
authors.initials: G
authors.lastname: Güebitz
authors.forename: Artur
authors.initials: A
authors.lastname: Cavaco-Paulo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005349:Fibroins / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D008422:Materials Testing; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D053491:Proteinase Inhibitory Proteins, Secretory / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013379:Substrate Specificity; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry
chemical_list: D010455:Peptides; D053491:Proteinase Inhibitory Proteins, Secretory; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D005349:Fibroins; D019272:Leukocyte Elastase