Anelli P L, Fedeli F, Gazzotti O, Lattuada L, Lux G, Rebasti F
Bracco spa, Milano Research Centre, via E. Folli 50, 20134 Milano, Italy.
Bioconjug Chem. 1999 Jan-Feb;10(1):137-40. doi: 10.1021/bc970212u.
Bisalkylation of suitably protected L-glutamic acid and L-lysine derivatives with tert-butyl N-(2-bromoethyl)iminodiacetate 2, followed by deprotection of the omega functional group affords N, N-bis[2-[bis[2-(1, 1-dimethylethoxy)-2-oxoethyl]amino]ethyl]-L-glutamic acid 1-(1, 1-dimethylethyl) ester 4 and N2,N2-bis[2-[bis[2-(1, 1-dimethylethoxy)-2-oxoethyl]amino]ethyl]-L-lysine 1,1-dimethylethyl ester 7. Such compounds feature a carboxylic or an amino group, respectively, which are available for conjugation with a suitable partner via formation of an amide bond. The conjugates, which can be prepared in this way, contain a chelating subunit in which all five acetic residues of DTPA are available for the complexation of metal ions. Direct bisalkylation of glycine with 2 promptly gives N, N-bis[2-[bis[2-(1,1-dimethylethoxy)-2-oxoethyl]amino]ethyl]glycine 11. The latter allows to achieve conjugates in which the central acetic group of DTPA is selectively converted into an acetamide.
用N-（2-溴乙基）亚氨基二乙酸叔丁酯2对适当保护的L-谷氨酸和L-赖氨酸衍生物进行双烷基化反应，然后对ω官能团进行脱保护，得到N，N-双[2-[双[2-（1,1-二甲基乙氧基）-2-氧代乙基]氨基]乙基]-L-谷氨酸1-（1,1-二甲基乙基）酯4和N2，N2-双[2-[双[2-（1,1-二甲基乙氧基）-2-氧代乙基]氨基]乙基]-L-赖氨酸1,1-二甲基乙酯7。这类化合物分别具有一个羧基或一个氨基，可通过形成酰胺键与合适的配体进行共轭。通过这种方式制备的共轭物含有一个螯合亚基，其中二乙三胺五乙酸（DTPA）的所有五个乙酸残基均可用于金属离子的络合。甘氨酸与2直接进行双烷基化反应可迅速得到N，N-双[2-[双[2-（1,1-二甲基乙氧基）-2-氧代乙基]氨基]乙基]甘氨酸11。后者可用于制备共轭物，其中DTPA的中心乙酸基团被选择性地转化为乙酰胺。
