Development of enzymatically cleavable prodrugs derived from dendritic polyglycerol.
In this Letter we report the synthesis and in vitro studies of cleavable polymer-drug conjugates derived from dendritic polyglycerol and maleimide-bearing prodrugs of doxorubicin and methotrexate that are cleaved by cathepsin B. Cleavage properties and cytotoxicity of the new conjugates are presented.
Calderón
Marcelo
M
Institut für Chemie und Biochemie, Freie Universität Berlin, Berlin, Germany.
Graeser
Ralph
R
Kratz
Felix
F
Haag
Rainer
R
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002401:Cathepsin B / Q000378:metabolism; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005990:Glycerol / Q000737:chemistry*; D006801:Humans; D008301:Maleimides / Q000737:chemistry; D008727:Methotrexate / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D050091:Dendrimers; D004337:Drug Carriers; D008301:Maleimides; D011108:Polymers; D011355:Prodrugs; C043592:maleimide; C043941:polyglycerol; D004317:Doxorubicin; D002401:Cathepsin B; D005990:Glycerol; D008727:Methotrexate