Three-dimensional structure-activity relationship study of belactosin A and its stereo- and regioisomers: development of potent proteasome inhibitors by a stereochemical diversity-oriented strategy

• Published in: Organic & biomolecular chemistry Vol. 7; no. 9; pp. 1868 - 1877
• Main Authors: Yoshida, Keisuke, Yamaguchi, Kazuya, Mizuno, Akira, Unno, Yuka, Asai, Akira, Sone, Takayuki, Yokosawa, Hideyoshi, Matsuda, Akira, Arisawa, Mitsuhiro, Shuto, Satoshi
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 01.01.2009
• Subjects: Cell Survival - drug effects; Chemistry; Chemistry, Organic; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; HeLa Cells; Humans; Isomerism; Models, Molecular; Molecular Structure; Peptides - chemical synthesis; Peptides - chemistry; Peptides - pharmacology; Physical Sciences; Proteasome Inhibitors; Science & Technology; Stereoisomerism; Structure-Activity Relationship; TARGET; CONFORMATIONAL RESTRICTION; ASYMMETRIC-SYNTHESIS; DRUG DEVELOPMENT; CYCLOPROPANATION; CELL-CYCLE; STEREOSELECTIVE-SYNTHESIS; PROTEOLYSIS; HISTAMINE; NF-KAPPA-B

The development of potent proteasome inhibitors based on the stereochemical diversity-oriented strategy using a conformationally rigid cyclopropane structure was investigated. Thus, a series of stereo- and regioisomeric analogs of belactosin A (2), a cyclopropane amino acid (methanoamino acid)-conta...