Application of strain-promoted azide-alkyne cycloaddition and tetrazine ligation to targeted Fc-drug conjugates.
Application of strain-promoted azide-alkyne cycloaddition and tetrazine ligation to targeted Fc-drug conjugates.
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将应变促进的叠氮化物环加成和四嗪连接的应用到靶向的FC-Crug con轭物中。
DOI：
10.1021/bc300052u
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发表时间：
2012-10-17
影响因子：
4.7
通讯作者：
Burke TR Jr
中科院分区：
文献类型：
--
作者：
Thomas JD;Cui H;North PJ;Hofer T;Rader C;Burke TR Jr
We have previously described an approach whereby antibody Fc fragments harboring a single C-terminal selenocysteine residue (Fc-Sec) are directed against a variety of targets by changing the peptide or small molecule to which they are conjugated. In the present work we describe methodology for improving the efficacy of these Fc-Sec conjugates by incorporating cytotoxic drugs. The Fc-Sec protein is first programmed to target specific tumor cell types by attachment of a bifunctional linker that contains a “clickable” handle (e.g. cyclobutane or cyclooctyne) in addition to a tumor cell-binding peptide or small molecule. Following Fc-Sec conjugation, a cytotoxic warhead is then attached by cycloaddition reactions of tetrazine or azide-containing linker. To validate this approach we used a model system in which folic acid (FA) is the targeting moiety and a disulfide-linked biotin moiety serves as a cytotoxic drug surrogate. We demonstrated successful targeting of Fc-Sec proteins to folate-receptor expressing tumor cells. Tetrazine ligation was found to be an efficient method for biotin “arming” of the folate-targeted Fc-Sec proteins. We also report novel bioconjugation methodologies that use [4+2] cycloaddition reactions between tetrazines and cyclootynes.
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影响因子：
46.2
作者：
Jewett JC;Bertozzi CR
通讯作者：
Bertozzi CR
影响因子：
15
作者：
Blackman, Melissa L.;Royzen, Maksim;Fox, Joseph M.
通讯作者：
Fox, Joseph M.
DOI：
10.1038/nri2744
发表时间：
2010-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.0800800105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Hofer, Thomas;Thomas, Joshua D.;Rader, Christoph
通讯作者：
Rader, Christoph
影响因子：
1.8
作者：
THALHAMMER, F;WALLFAHRER, U;SAUER, J
通讯作者：
SAUER, J