title: Miniature bovine pancreatic trypsin inhibitors (m-BPTIs) of the West Nile virus NS2B-NS3 protease.
abstract: The mosquito-borne West Nile virus (WNV) causes a wide range of symptoms ranging from fever to the often fatal viral encephalitis. To date, no vaccine or drug therapy is available. The trypsin-like WNV NS2B-NS3 protease is deemed a plausible drug target and was shown to be inhibited by bovine pancreatic trypsin inhibitor (BPTI), a 58-residue protein isolated from bovine lung. Herein, we report a protein truncation study that resulted in a novel 14-residue cyclic peptide with equipotent inhibitory activity to native BPTI. We believe our truncation strategy can be further applied in the development of peptide-based inhibitors targeting trypsin-like proteases.
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Melgious J Y
authors.initials: MJ
authors.lastname: Ang
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Huichang A
authors.initials: HA
authors.lastname: Lim
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Anders
authors.initials: A
authors.lastname: Poulsen
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: John Liang Kuan
authors.initials: JL
authors.lastname: Wee
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Fui Mee
authors.initials: FM
authors.lastname: Ng
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Joma
authors.initials: J
authors.lastname: Joy
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hill
authors.affiliation: a Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR) , Singapore , Singapore.
authors.forename: C S Brian
authors.initials: CS
authors.lastname: Chia
mesh_terms: D000818:Animals; D002417:Cattle; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism; D013329:Structure-Activity Relationship; D014357:Trypsin / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014902:West Nile virus / Q000187:drug effects / Q000201:enzymology*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D011480:Protease Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D014357:Trypsin; D014361:Trypsin Inhibitors; D017361:Viral Nonstructural Proteins; C080102:NS2B protein, flavivirus; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: Aprotinin; BPTI; NS3 protease; West Nile virus; peptide