Chemical and synthesis of novel peptide-2,6-dimethoxyhydro- ptoacetic acids conjugates

• Main Authors: Chuang,Ming-Ju, 莊名朱
• Other Authors: Mr. Sheh,Leung
• Format: Others
• Language: zh-TW
• Published: 1994
• Online Access: http://ndltd.ncl.edu.tw/handle/29733678958946695363

碩士 === 東海大學 === 應用化學系 === 82 === This thesis reports the synthesis of two groups of new drugs which are the conjugates of linear dipeptides and the cytotoxic agent 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid(DMQ-MA). The first group is DMQ-MA-X-Arg-OMe(X=Ala,Val, Phe,Thr).Since the charge density of malignant cell surface is different from that of normal cells,the peptides containing positive charge amino acid residues like Arg may bind to malignant. Since the index of cytotoxicity of DMQ-MA-glycineamide is 40 times lower than that of DMQ-MA,120 times lower than that of DMQ-MA- alanineamide,thus,it is logical to synthesize the dipeptides containing glycinamide carriers of DMQ-MA. We also investigate the possibility of using enzymatic reactions for the synthesis of these conjugates. The enzyme chosen is alcalase. In the enzymatic reactions DMQ-MA-Y-methly ester (Y =glycine,alanine, phenylalanine, tyrosine) are chosen as acyl donors where as glycinamide, alanineamide, leucineamide, and glycine- alanineamide, glycine-leucineamide and alanine-phenyl- alanineamide are chosen as nucleophiles. It is found that DMQ- MA-Gly-Gly-NH2,DMQ-MA-Gly-Ala-NH2,DMQ-MA-Ala-Ala-NH2,DMQ-MA- Ala-Leu-NH2,DMQ-MA-Ala-Gly-Leu-NH2 and DMQ-MA-Phe-Ala-NH2 can be successfully synthesized by the alcalase method.