Azido-dPEG®₄-NHS ester

Azido-dPEG®4-NHS ester, product number 10501, contains an azide group linked to an N-hydroxysuccinimidyl (NHS) ester through a single molecular weight, discrete polyethylene glycol (dPEG®) spacer. This product works with copper(I)-catalyzed or ruthenium-catalyzed click chemistry and with copper free click chemistry using Quanta BioDesign's line of DBCO-functionalized dPEG® products. The dPEG® spacer imparts water solubility and adds hydrodynamic volume to the conjugated product. The single molecular weight product design, with its discrete chain length, simplifies analysis of this product.

NHS esters are the most popular, most widely used way to conjugate carboxylic acids to primary or secondary amines resulting in stable amide bonds. NHS esters react quickly and efficiently in aqueous media at physiological pH values (7.0 – 7.5). However, they are prone to hydrolysis over time. Moreover, the rate of hydrolysis is pH dependent. Consequently, they must be used immediately upon dissolution in water or aqueous buffer. Published research as well as work done internally by Quanta BioDesign has shown that 2,3,5,6-tetrafluorophenyl (TFP) esters are more hydrolytically stable and have better reactivity than NHS esters.

Barry Sharpless and colleagues defined the rapid, chemoselective, stereospecific reactions between an azide and an alkyne leading to the formation of a triazole ring as click chemistry. From its publication 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). Subsequently, 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.

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 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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