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Extensive Range of Coupling Reagents and Linkers

Within its comprehensive Novabiochem® product line, Merck offers one of the most extensive ranges of high-quality coupling reagents for in situ activation on the market. Moreover, we provide additives, linkers for solid phase synthesis, and various reagents for the introduction of protecting groups. Thus you can be sure to find the right reagents even for your most demanding applications.

However, with such a plethora of reagents available, the choice of the optimum coupling reagent for a particular application is not always straightforward. Condensation reagents vary in terms of coupling efficiency, stability, solubility, or reactivity of active species (see table below). For example, PyOxim combines high reactivity and solubility with moderate stability, making it an excellent choice for synthesizers employing closed-bottle reagent storage.

In order to help you choosing the appropriate reagent for your individual application, we have prepared for you the technical brochure “Coupling reagents for peptide synthesis” with valuable information on our coupling reagents and detailed methods and protocols (to download the brochure click on the banner on the right).

Finding the Perfect Coupling Agent

To simplify your reagent selection, the following table summarizes the properties and advantages of the most commonly used coupling reagents.

Coupling reagent
Solubility (M)
Stability in DMF closed vial
Reactivity of active species
BOP >1.5 n/a 4 Water soluble by-products make it useful for solution phase synthesis
COMU 1.5 low 2 High reactivity but very limited solution stability
DEPBT n/a n/a 4 Excellent reagent for coupling for protected fragments with low racemization
HATU 0.45 excellent 1 Gold standard for coupling of hindered couplings, but expensive compared to other reagents
HBTU 0.5 excellent 4 Excellent reagent for routine synthesis. May cause guanidinylation
HCTU 0.75 excellent 3 More reactive and expensive than HBTU. May cause guanidinylation
PyAOP  >1.5 low to moderate 1 Ideal for hindered couplings, and mediating fragment condensation and cyclization reagents. Does not cause guanidinylation
PyBOP® >1.5 moderate 4 Excellent reagent for routine synthesis. Ideal for in situ activation as it does not cause guanidinylation
PyOxim >1.5 moderate 2 Similar advantages to PyBOP but generates a more reactive active species
TSTU n/a n/a 5 For production of OSu esters, for active ester coupling in water

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