DOTA-tris(TBE)-amido dPEG®₁₁-MAL

DOTA-tris(TBE)-amido-dPEG®11-MAL, product number 11166, is a thiol-reactive DOTA compound containing a single molecular weight, discrete polyethylene glycol (dPEG®) spacer between the DOTA and the maleimide groups. The macrocyclic DOTA moiety is protected with tert-butyl ester (TBE) groups on the four acetate units. The maleimide group reacts with free thiol groups in a click chemistry type of reaction known as the thiol-Michael addition reaction.

The macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a highly popular, effective bifunctional chelator that is used in radiopharmaceutical applications that require trivalent isotopes of yttrium or lanthanides. This form of DOTA has the four acetate groups protected with tert-butyl esters (TBE). This intermediate DOTA form is not an effective chelator, but it is useful in situations where the DOTA needs to be incorporated into the molecule at an early stage of development.

Traditional PEG is a disperse (Đ > 1) polymer. Over the past several years research has proven that large, disperse PEG is not always needed and in many cases may work against the intended goals of PEGylation by, for example, reducing ligand affinity for a receptor or inhibiting cell internalization. By contrast, Quanta BioDesign produces only single molecular weight (that is, discrete) PEG products (that is, Đ = 1). Our smaller dPEG® products avoid problems associated with large PEGs. The discrete character of our products simplifies analysis of the dPEG® product and of conjugates formed with dPEG® products.

The maleimide group is widely used to conjugate molecules to free thiols or sulfhydryls. The very fast reaction between a maleimide group and a free thiol or sulfhydryl group is a classic example of the thiol-Michael addition reaction.

If you need bulk product in a larger package size than our standard sizes, please contact us for a quote. Our commercial capabilities permit us to manufacture this product at any scale that you need.

Application References:

Hermanson, G. T. Chapter 2, Functional Targets for Bioconjugation. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 127-228, specifically pages 191-192, discussing iodoacetates and bromoacetates reacting with thiols.
Hermanson, G. T. Chapter 3, The Reactions of Bioconjugation. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 229-258, specifically page 241, discussing maleimide reactions.
Hermanson, G. T. Chapter 12, Isotopic Labeling Techniques. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 507-534, specifically pages 508-509, discussing DOTA.
Hermanson, G. T. Chapter 18, PEGylation and Synthetic Polymer Modification. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 787-838.
De León-Rodríguez, L. M.; Kovacs, Z. The Synthesis and Chelation Chemistry of DOTA−Peptide Conjugates. Bioconjugate Chem. 2008, 19(2), 391–402. https://doi.org/10.1021/bc700328s.
Brechbiel, M. W. Bifunctional chelates for metal nuclides. The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2008, 52(2), 166-173. https://www.minervamedica.it/en/journals/nuclear-med-molecular-imaging/article.php?cod=R39Y2008N02A0166 (accessed Feb 7, 2019).
Nair, D. P.; Podgórski, M.; Chatani, S.; Gong, T.; Xi, W.; Fenoli, C. R.; Bowman, C. N. The Thiol-Michael Addition Click Reaction: A Powerful and Widely Used Tool in Materials Chemistry. Chem. Mater. 2014, 26(1), 724–744. https://doi.org/10.1021/cm402180t.
Sun, Y.; Liu, H.; Cheng, L.; Zhu, S.; Cai, C.; Yang, T.; Yang, L.; Ding, P. Thiol Michael Addition Reaction: A Facile Tool for Introducing Peptides into Polymer-Based Gene Delivery Systems. Polymer International 2018, 67(1), 25–31. https://doi.org/10.1002/pi.5490.
Northrop, B. H.; Frayne, S. H.; Choudhary, U. Thiol–maleimide "click" chemistry: evaluating the influence of solvent, initiator, and thiol on the reaction mechanism, kinetics, and selectivity. Polymer Chemistry 2015, 6, 3415-3430. https://doi.org/10.1039/C5PY00168D.

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