DOTA-tris(acid)-amido-dPEG®3-bromoacetamide, product number 11150, combines the macrocycle 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) through a single molecular weight, discrete polyethylene glycol (dPEG®) linker to a bromoacetyl moiety that couples to the dPEG® linker via an amide bond. The linker contains 14 atoms and is 15.6 Å long from the terminal amide adjacent to the DOTA moiety to the methylene moiety adjacent to the bromine atom.
DOTA is a highly popular bifunctional chelator. It is used in a variety of diagnostic and therapeutic applications for the delivery of radionuclides, particularly yttrium and radionuclides in the lanthanide series. For treatments using trivalent yttrium or trivalent lanthanides, DOTA is the preferred ligand because it forms thermodynamically stable, kinetically inert complexes.
The bromoacetyl moiety (present as the bromoacetamide in PN11150) reacts selectively, but not specifically, with free thiol groups. The reaction forms stable thiol ether bonds. The rate and specificity of bromoacetyl for free thiols depends upon the pH of the reaction and the relative availability (compared to thiols) of other groups with which the bromoacetyl moiety can react. For more information on the bromoacetyl-thiol reaction, please see Bromoacetyl Reaction Chemistry.
The short, single molecular weight dPEG® linker between the DOTA and the bromoacetyl groups serves many purposes. It provides flexibility to the entire molecule. Because each ethylene glycol unit in the dPEG® chain hydrogen bonds up to three molecules of water, the molecule gains water solubility, and in aqueous environments such as blood, it increases the hydrodynamic volume of the molecule and of anything to which the molecule is conjugated. With larger hydrodynamic volume, conjugates are less susceptible to renal excretion, which means that lower doses of the diagnostic or therapeutic agent are needed for the conjugate to affect its purpose. Moreover, dPEG® is non-immunogenic, and its large hydrodynamic volume helps reduce the immunogenicity of molecules to which it is conjugated. More information about our dPEG® products can be found here and here.
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.
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. Click here now for a review of Greg’s book and a link to purchase it.
Hermanson, G. T. Chapter 18, PEGylation and Synthetic Polymer Modification. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 787-838.
Hermanson, G. T. Chapter 21, Liposome Conjugates and Derivatives. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, 921-949.
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.
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