[The solid-phase synthesis of methotrexate-alpha-peptides].
Methotrexate(MTX) and the methotrexate-alpha-peptides(MTX-alpha-phenylalanine and MTX-alpha-arginine i.e. MTX-alpha-Phe and MTX-alpha-Arg) were prepared with the technique of solid-phase peptide synthesis. Its purity was verified as a single peak by HPLC and its molecular weight was measured by mass spectrometry. MTX-alpha-Phe could be hydrolyzed to MTX by carboxypeptidase A. The cytotoxic effect of released MTX was found to be 100 times stronger than that of the peptide in vitro. It is suggested that MTX-alpha-Phe is a satisfactory prodrug in the treatment of cancer.
Shi
P T
PT
Shanghai Institute of Biochemistry, Chinese Academy of Sciences, Shanghai 200031.
Hao
X K
XK
Chen
Y
Y
Zhang
Y H
YH
Tao
Q Y
QY
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D049691:History, Medieval; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis*; D011471:Prostatic Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011355:Prodrugs; C091716:methotrexate-alpha-phenylalanine; C066905:methotrexate-alpha-arginine; D010649:Phenylalanine; D008727:Methotrexate