Doxorubicin immunoconjugates containing bivalent, lysosomally-Cleavable dipeptide linkages

Autor:	Michael A. Walker, Shilpa Radia, Dalton King, Shirley J. Lasch, David Willner, Hofstead Sandra J, Gene M. Dubowchik, Harold Mastalerz, Raymond A. Firestone, Pamela A. Trail
Rok vydání:	2002
Předmět:	Immunoconjugates Lung Neoplasms medicine.drug_class Stereochemistry media_common.quotation_subject Clinical Biochemistry Pharmaceutical Science Peptide Monoclonal antibody Biochemistry Cathepsin B Inhibitory Concentration 50 chemistry.chemical_compound Drug Discovery Tumor Cells Cultured medicine Humans Doxorubicin Sulfhydryl Compounds Internalization Molecular Biology media_common chemistry.chemical_classification Binding Sites Dipeptide Organic Chemistry Antibodies Monoclonal Stereoisomerism Biological activity Dipeptides Immunoconjugate chemistry Chromatography Gel Molecular Medicine Lysosomes Dimerization Half-Life Conjugate medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 12:1529-1532
ISSN:	0960-894X
DOI:	10.1016/s0960-894x(02)00194-4
Popis:	Bivalent doxorubicin (DOX)-dipeptides ( 16a – c ) were prepared and conjugated to the monoclonal antibody BR96. The dipeptides are cleaved by lysosomal proteases following internalization of the resulting immunoconjugates. Conjugate 18b demonstrated antigen-specific in vitro tumor cell killing activity (IC 50 =0.2 μM) that was equipotent to DOX with a near doubling of drug molecules/MAb. Size exclusion chromatography showed 18b to be a noncovalent dimer that was formed immediately upon conjugation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::933401d420d7b01374ef7d812e2fa84b https://doi.org/10.1016/s0960-894x(02)00194-4 Zobrazit plný text záznamu Full Text from ScienceDirect