Article ID Journal Published Year Pages File Type
1395622 European Journal of Medicinal Chemistry 2014 10 Pages PDF
Abstract

•HIV-1 protease and Candida albicans Sap2 share structural similarity.•A library of Sap2-active bicyclic peptidomimetics was assayed toward HIV protease.•Synthesis of a pool of tripeptide mimetics to expand the library.•Two compounds with inhibition in low micromolar range were selected.•4-Benzyl-peptidomimetics addressed S1′ subsite with the Phe side-chain isostere.

Small-molecule peptidomimetic inhibitors that already showed activity towards Secreted aspartic protease 2 as anti-Candida agents are herein presented as candidate HIV protease inhibitors. A library of 6,8-dioxa-3-azabicyclo[3.2.1]-octane peptidomimetic scaffolds was screened towards HIV protease, resulting in the identification of hit compounds possessing IC50 in the sub-micromolar range, and showing the bicyclic acetal portion as a potential transition state analogue in the interaction with catalytic aspartic acid residues.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
Authors
, , ,