Azido-dPEG®₃₆-TFP ester

Azido-dPEG®36-TFP ester, product number 10573, is a crosslinking compound designed for copper(I)-catalyzed, ruthenium-catalyzed, and strain promoted click chemistry. The azide group provides the click chemistry functionality. The 2,3,5,6-tetrafluorophenyl (TFP) ester offers excellent reactivity for primary and secondary amines. An extended, single molecular weight, discrete polyethylene glycol (dPEG®) spacer separates the reactive groups at each end of the molecule. The spacer imparts water solubility to Azido-dPEG®36-TFP ester and increases the hydrodynamic volume of the molecule. Moreover, the azide group on Azido-dPEG®36-TFP ester can act as a masked amine that reacts with carboxylic acid groups after reduction to a primary amine.

Traditional PEGylation Reagents and dPEG® Products
PEGylation is the process of modifying biomolecules and surfaces with polyethylene glycol (PEG). Traditionally, PEG products are non-uniform, disperse polymers comprised of multiple, different chain lengths of PEG, with each chain having a different molecular weight. The stated sizes of conventional PEG products are averages of the various chain lengths and molecular weights of PEG in the polymer mixture.

Ourproducts consist of discrete chain lengths of PEG. With only one chain length, the product has a single molecular weight. Thus, our PEG products are called "discrete PEG" products. Therefore, we sell them under the dPEG® tradename.

TFP Esters Compared to NHS Esters
TFP esters are a superior alternative to the widely popular N-hydroxysuccinimidyl (NHS) esters. TFP esters are more hydrolytically stable than NHS esters, especially at high pH values (≥ 8) where NHS esters in aqueous solution have half-lives measured in minutes. Also, TFP esters react more efficiently with primary and secondary amines than NHS esters.

Click Chemistry and dPEG® Products
From the first report by K. Barry Sharpless and colleagues in 2001, click chemistry has grown consistently in popularity and importance for the development of new chemical structures. The first-reported click chemistry reactions were catalyzed by copper(I) and are known as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Classical CuAAC chemistry forms a 1,4-disubstituted triazole ring. Ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) operates similarly to CuAAC but gives rise to 1,5-disubstituted triazole rings. Later, copper-free click chemistry (formally known as strain promoted azide-alkyne cycloaddition, or SPAAC) was developed by Carolyn Bertozzi and colleagues to facilitate click chemistry reactions in living cells without the use of toxic copper salts.

Application References:

Hermanson, G. T. Chapter 3, The Reactions of Bioconjugation. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, pp 229-258, especially pages 233-234 (NHS esters) and pages 238-239 (fluorophenyl esters).
Hermanson, G. T. Chapter 17, Chemoselective Ligation; Bioorthogonal Reagents. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, pp 757-786, particularly pages 769-775 where click chemistry is discussed.
Hermanson, G. T. Chapter 18, PEGylation and Synthetic Polymer Modification. Bioconjugate Techniques, 3rd edition. Academic Press: New York, 2013, pp 787-838.
Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Click Chemistry: Diverse Chemical Function from a Few Good Reactions. Angew. Chem. Int. Ed., 2001, 40, 2004-2021. https://doi.org/10.1002/1521-3773(20010601)40:11%3C2004::AID-ANIE2004%3E3.0.CO;2-5
Kolb, H. C.; Sharpless, K. B. The growing impact of click chemistry on drug discovery. Drug Disc. Today, 2003, 8(24), 1128-1137. https://doi.org/10.1016/S1359-6446(03)02933-7.
Baskin, J. M.; Bertozzi, C. R. Bioorthogonal Click Chemistry: Covalent Labeling in Living Systems. QSAR & Combinatorial Science 2007, 26(11–12), 1211–1219. https://doi.org/10.1002/qsar.200740086.
Patterson, D. M.; Nazarova, L. A.; Prescher, J. A. Finding the Right (Bioorthogonal) Chemistry. ACS Chem. Biol. 2014, 9(3), 592–605. https://doi.org/10.1021/cb400828a.
Dommerholt, J.; Rutjes, F. P. J. T.; van Delft, F. L. Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides. Top. Curr. Chem. (Z) 2016, 374(2), 16. https://doi.org/10.1007/s41061-016-0016-4.
Johansson, J. R.; Beke-Somfai, T.; Said Stålsmeden, A.; Kann, N. Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications. Chem. Rev. 2016, 116(23), 14726–14768. https://doi.org/10.1021/acs.chemrev.6b00466.

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