title: Design and regioselective synthesis of a new generation of targeted chemotherapeutics. Part II: Folic acid conjugates of tubulysins and their hydrazides.
abstract: Efficient syntheses of folate conjugates of tubulysins and their hydrazides 1a-d are described. These water soluble folate receptor (FR) targeted conjugates are derivatives of folic acid and the potent cytotoxic agents: tubulysin A, B, or their respective hydrazides, connected in regioselective manner via a hydrophilic peptide spacer and a reducible disulfide linker.
authors.affiliation: Endocyte Inc., 3000 Kent Avenue, Suite A1-100, West Lafayette, IN 47906, USA. ivlahov@endocyte.com
authors.forename: Iontcho R
authors.initials: IR
authors.lastname: Vlahov
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kleindl
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Leamon
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004220:Disulfides / Q000737:chemistry; D004229:Dithiothreitol / Q000737:chemistry; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D008956:Models, Chemical; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D004220:Disulfides; D058973:Folate Receptors, GPI-Anchored; D006834:Hydrazines; D009842:Oligopeptides; D010455:Peptides; D011956:Receptors, Cell Surface; C510756:tubulysin A; D005492:Folic Acid; D004229:Dithiothreitol