Evaluation of a structure-based statine cyclic diamino amide encoded combinatorial library against plasmepsin II and cathepsin D

• Published in: Bioorganic & medicinal chemistry letters Vol. 8; no. 22; pp. 3203 - 3206
• Main Authors: Carroll, Carolyn DiIanni, Johnson, Theodore O., Tao, Shewei, Lauri, Giorgio, Orlowski, Marc, Gluzman, Ilya Y., Goldberg, Daniel E., Dolle, Roland E.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 17.11.1998; Elsevier
• Subjects: Amides - pharmacology; Amino Acids - pharmacology; Analytical, structural and metabolic biochemistry; Aspartic Acid Endopeptidases - antagonists & inhibitors; Biological and medical sciences; Cathepsin D - antagonists & inhibitors; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Hydrolases; Protease Inhibitors - pharmacology; Protozoan Proteins; Structure-Activity Relationship; Aminoalcohol; Enzyme; Plasmepsin II; Combinatorial chemistry; Enzyme inhibitor; Non peptide compound; Selectivity; In vitro; Peptidases; Structure activity relation; Chemical compound library; Hydrolases; Aspartic endopeptidases; Cathepsin D; Solid phase; Piperazine derivatives; Chemical synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(98)00554-X

A structure-based 18,900-member combinatorial library was synthesized containing a statine template and three cyclic diamino acids as potential P 1′, P 2–P 4 surrogates. Evaluation of this encoded library against two aspartyl proteases, plasmepsin II and cathepsin D, led to the identification of selective inhibitors for each enzyme. Selective inhibitors of plasmepsin II and cathepsin D were identified from an encoded 18,900-member combinatorial library.