BTTAA,a (Cu(I)) ligand stabilizer and catalyst,can enhances bioorthogonal click reactions and reduces cytotoxicity by lowering the amount of copper ions used. BTTAA can be used with azide to label and detect azide-labeled complexes in Jurkat cells, zebrafish, and bacteria [1.3].
Experimental proof that 50 μM BTTAA-Cu(I) complex have no effect on cell viability[2]. BTTAA-Cu(I) catalyst provided the strongest labeling of the SiaNAz-displaying cells, yielding cell-associated Alexa Fluor 488 signal 3 to 4-fold higher than the signal achieved[3] .Cu-BTTAA performs significantly better as a catalyst than Cu-THPTA or Cu-TBTA. BTTAA has been shown to perform much better than THPTA or TBTA [4.5].
References:
[1] Haldón E, Nicasio MC, Pérez PJ. Copper-catalysed azide-alkyne cycloadditions (CuAAC): an update. Org Biomol Chem. 2015 Oct 7;13(37):9528-50.
[2] Yang M, Yang Y, Chen PR. Transition-Metal-Catalyzed Bioorthogonal Cycloaddition Reactions. Top Curr Chem (Cham). 2016 Feb;374(1):2.
[3]Besanceney-Webler C, Jiang H, Zheng T, Feng L, Soriano del Amo D, Wang W, Klivansky LM, Marlow FL, Liu Y, Wu P. Increasing the efficacy of bioorthogonal click reactions for bioconjugation: a comparative study. Angew Chem Int Ed Engl. 2011 Aug 22;50(35):8051-6.
[4] Besanceney-Webler C, Jiang H, Zheng T, Feng L, Soriano del Amo D, Wang W, Klivansky LM, Marlow FL, Liu Y, Wu P. Increasing the efficacy of bioorthogonal click reactions for bioconjugation: a comparative study. Angew Chem Int Ed Engl. 2011 Aug 22;50(35):8051-6.
[5] Loh CT, Ozawa K, Tuck KL, Barlow N, Huber T, Otting G, Graham B. Lanthanide tags for site-specific ligation to an unnatural amino acid and generation of pseudocontact shifts in proteins. Bioconjug Chem. 2013 Feb 20;24(2):260-8.