DOTA-tris(acid)-amido-dPEG®11-bromoacetamide, product number 11152, 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 bromoacetate moiety that couples to the dPEG® linker via an amide bond. The linker contains 38 atoms and is 43.9 Å long from the terminal amide adjacent to the DOTA moiety to the methylene group adjacent to the bromine atom.
The bromoacetate moiety (present as the bromoacetamide in PN11152) reacts selectively, but not specifically, with free thiol groups. The reaction forms stable thiol ether bonds. The rate and specificity of bromoacetate for free thiols depends upon the pH of the reaction and the relative availability (compared to thiols) of other groups with which the bromoacetate moiety can react.
DOTA is a highly popular bifunctional chelator. It is used in a variety of diagnostic and therapeutic applications for the delivery of radionuclides, particularly radionuclides in the lanthanide series and yttrium, which has similar chemical behavior. DOTA is the preferred ligand for treatments using trivalent lanthanides or yttrium, because DOTA binds the metal ions to form complexes that are thermodynamically stable and kinetically inert.
The medium-length, single molecular weight dPEG® linker between the DOTA and the bromoacetate groups serves many purposes. First, each ethylene glycol unit in the dPEG® chain acquires up to three molecules of water through hydrogen bonding. Consequently, the molecule gains water solubility. Second, in aqueous environments such as blood, dPEG® 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. Third, dPEG® linkers and spacers provide flexibility to the entire molecule. Fourth, 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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