title: Site-specific traceless coupling of potent cytotoxic drugs to recombinant antibodies for pharmacodelivery.
abstract: Aldehyde drugs are gaining increasing research interest, considering that aldehyde dehydrogenases overexpression is characteristic of cancer stem cells. Here, we describe the traceless site-specific coupling of a novel potent drug, containing an aldehyde moiety, to recombinant antibodies, which were engineered to display a cysteine residue at their N-terminus, or a 1,2-aminothiol at their C-terminus. The resulting chemically defined antibody-drug conjugates represent the first example in which a thiazolidine linkage is used for the targeted delivery and release of cytotoxic agents.
authors.affiliation: Philochem AG, Libernstrasse 3, CH-8112 Otelfingen, Switzerland.
authors.forename: Giulio
authors.initials: G
authors.lastname: Casi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Huguenin-Dezot
authors.forename: Kathrin
authors.initials: K
authors.lastname: Zuberbühler
authors.forename: Jörg
authors.initials: J
authors.lastname: Scheuermann
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
mesh_terms: D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D055808:Drug Discovery; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry*; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000447:Aldehydes; D000906:Antibodies; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D009842:Oligopeptides; D011994:Recombinant Proteins; D013438:Sulfhydryl Compounds; C094621:cemadotin