DOTA-tris(acid)-amido-dPEG®₁₁-Maleimide

DOTA-tris(acid)-amido-dPEG®11-maleimide, product number 11167, links a thiol-reactive maleimide group with the macrocyclic, bifunctional chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) through a medium-length, single molecular weight, discrete PEG (dPEG®) linker. The DOTA moiety is designed to chelate trivalent yttrium and trivalent elements in the lanthanide series. The maleimide group reacts chemoselectively with thiols at pH 6.5 – 7.5 in a click chemistry type of reaction.

Traditional PEG is a dispersed (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.

DOTA is a highly popular, effective bifunctional chelator that is used in radiopharmaceutical applications that require trivalent isotopes of yttrium or lanthanides. The four acetate groups on the macrocycle are unprotected. Therefore, this DOTA compound should be conjugated to the target molecule at the end of the synthetic process when no further reactions will be carried out.

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, which is a specific, click chemistry type of the 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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