title: Peptide inhibitors of Dengue virus NS3 protease. Part 1: Warhead.
abstract: Substrate-based tetrapeptide inhibitors with various warheads were designed, synthesized, and evaluated against the Dengue virus NS3 protease. Effective inhibition was achieved by peptide inhibitors with electrophilic warheads such as aldehyde, trifluoromethyl ketone, and boronic acid. A boronic acid has the highest affinity, exhibiting a K(i) of 43 nM.
authors.affiliation: Novartis Institute for Tropical Diseases, 10 Biopolis Road, 05-01 Chromos, Singapore 138670, Singapore. zheng.yin@novartis.com
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yin
authors.forename: Sejal J
authors.initials: SJ
authors.lastname: Patel
authors.forename: Wei-Ling
authors.initials: WL
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Wai-Ling
authors.initials: WL
authors.lastname: Chan
authors.forename: K R Ranga
authors.initials: KR
authors.lastname: Rao
authors.forename: Jenefer
authors.initials: J
authors.lastname: Alam
authors.forename: Duraiswamy A
authors.initials: DA
authors.lastname: Jeyaraj
authors.forename: Xinyi
authors.initials: X
authors.lastname: Ngew
authors.forename: Viral
authors.initials: V
authors.lastname: Patel
authors.forename: David
authors.initials: D
authors.lastname: Beer
authors.forename: Siew Pheng
authors.initials: SP
authors.lastname: Lim
authors.forename: Subhash G
authors.initials: SG
authors.lastname: Vasudevan
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Keller
mesh_terms: D001897:Boronic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003716:Dengue Virus / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007659:Ketones / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry; D013379:Substrate Specificity; D013997:Time Factors; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D001897:Boronic Acids; D004791:Enzyme Inhibitors; D007659:Ketones; D010455:Peptides; D011480:Protease Inhibitors; D020365:RNA Helicases; D012697:Serine Endopeptidases; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases