title: Synthesis and biological evaluation of tubulysin D analogs related to stereoisomers of tubuvaline.
abstract: The synthesis and biological evaluation of stereoisomers in tubulysin D are described. The stereoselective synthesis of all possible stereoisomers of C-11 and C-13 positions in tubulysin D was achieved by employing 1'-epi-Tuv-Me, 3'-epi-Tuv-Me, and ent-Tuv-Me and their biological properties were evaluated. It is clear that the stereochemistries of the C-11 and C-13 positions in tubulysin D have no practical impact on the inhibition of tubulin polymerization but play a role in the potent antiproliferative activities.
authors.affiliation: Exploratory Research Laboratories, Kyorin Pharmaceutical Co Ltd, 2399-1 Nogi, Nogi-Machi, Shimotsuga-Gun, Tochigi 329-0114, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Shibue
authors.forename: Iwao
authors.initials: I
authors.lastname: Okamoto
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morita
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hirasawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hosoya
authors.forename: Osamu
authors.initials: O
authors.lastname: Tamura
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D014404:Tubulin; D050257:Tubulin Modulators; C502386:tubulysin D