| Summary: | 碩士 === 東海大學 === 應用化學系 === 81 === This thesis reports the synthesis of two groups of new
antitumor drugs which are the conjugates of linear dipeptides
and the cyto-toxic agent DMQ-MA。The first group is: DMQ-MA-Gly
-Gly-NH, DMQ-MA-β-Ala-Gly-NH, DMQ-MA-Ala-Gly-NH, DMQ-MQ-
Val-Gly-NH。 Since the ICof DMQ-MA-Gly-NH is 40 times lower
than that of DMQ-MA, 120 times lower than that of DMQ-MA-Ala-NH
,thus ,it is logical to synthesize the dipeptides containing
Gly-NHas drug carriers of DMQ-MA。 We also investigate the
possibility of using enzymatic reactions for the synthesis of
these conjugates。In the enzymatic reactions DMQ-MA-Ala-OMe,
DMQ-MA-Val-OMe, DMQ-MA-Phe-OMe and DMQ-MA-Arg-OMe are chosen as
acyl donors and Gly-NH ,Ala-NH ,and Phe-NH are nucleophiles。
The enzyme chosen is alcalase。Only DMQ-MA-Ala-Gly-NHand DMQ-
MA-Phe-Gly-NH can be sucessfully synthesized by the alcalase
method, and the yield is lower than that of organic synthesis。
The second group is DMQ-MA-Gly-Arg-OMe, DMQ-MA-β -Ala-Arg-OMe,
DMQ-MA-Gaba-Arg-OMe and DMQ-MA-Ile-Arg-OMe。 Since the charge
density of malignant cell surface is different from that of
normal cells , the peptides containing positive charge amino
acid like Arg may bind to malignant cells more efficiently than
DMQ-MA itself.
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