Peptide inhibitors of dengue virus NS3 protease. Part 2: SAR study of tetrapeptide aldehyde inhibitors.

Basic Information

ID: ALA1147782

Journal: Bioorg Med Chem Lett

Title: Peptide inhibitors of dengue virus NS3 protease. Part 2: SAR study of tetrapeptide aldehyde inhibitors.

Authors: Yin Z, Patel SJ, Wang WL, Chan WL, Ranga Rao KR, Wang G, Ngew X, Patel V, Beer D, Knox JE, Ma NL, Ehrhardt C, Lim SP, Vasudevan SG, Keller TH.

Abstract: With the aim of discovering potent and selective dengue NS3 protease inhibitors, we systematically synthesized and evaluated a series of tetrapeptide aldehydes based on lead aldehyde 1 (Bz-Nle-Lys-Arg-Arg-H, K(i)=5.8 microM). In general, we observe that interactions of P(2) side chain are more important than P(1) followed by P(3) and P(4). Tripeptide and dipeptide aldehyde inhibitors also show low micromolar activity. Additionally, an effective non-basic, uncharged replacement of P(1) Arg is identified.

CiteXplore: 16246563

DOI: 10.1016/j.bmcl.2005.09.049

Patent ID: