Author/Authors :
Gene M. Dubowchik، نويسنده , , Shilpa Radia، نويسنده , , Harold Mastalerz، نويسنده , , Michael A. Walker، نويسنده , , Raymond A. Firestone، نويسنده , , H. Dalton King، نويسنده , , Sandra J. Hofstead، نويسنده , , David Willner، نويسنده , , Shirley J. Lasch، نويسنده , , Pamela A. Trail، نويسنده ,
Abstract :
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 (IC50=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.
