Beta-cyclodextrin/epoxysuccinyl peptide conjugates: a new drug targeting system for tumor cells.
Beta-cyclodextrin is known to form inclusion complexes with hydrophobic drugs. Several tumor cell lines are known to secrete and/or contain membrane-associated cathepsin B which is possibly involved in invasion and metastasis. Based on these information, our recently developed endo-epoxysuccinyl peptide inhibitor MeO-Gly-Gly-Leu-(2S,3S)-tEps-Leu-Pro-OH for cathepsin B was conjugated with beta-cyclodextrin to obtain a site-directed drug carrier system. Furthermore, the conjugate, was shown to form an inclusion complex with the cytotoxic drug methotrexate.
Schaschke
N
N
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Assfalg-Machleidt
I
I
Machleidt
W
W
Lassleben
T
T
Sommerhoff
C P
CP
Moroder
L
L
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D003505:Cyclodextrins / Q000138:chemical synthesis / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D047392:beta-Cyclodextrins
D000964:Antimetabolites, Antineoplastic; D003505:Cyclodextrins; D004337:Drug Carriers; D004852:Epoxy Compounds; D010455:Peptides; D047392:beta-Cyclodextrins; C031215:betadex; D008727:Methotrexate