Coupling reagents and methods

COUPLING REAGENTS AND METHODS FOR SOLID-PHASE SYNTHESIS... 

For the immobilization of biomolecules onto the functionalized surfaces, a wide range of different coupling reagents and methods is available [32], Defining some general conditions and requirements prior to immobilization is helpful to find and optimize the best suited and most feasible way for the specific application in mind. 

The reagents and methods employed for coupling in solid-phase synthesis are the same as for synthesis in solution, but a few are excluded because they are unsuitable. The mixed-anhydride method (see Section 2.6) and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline (see Section 2.15) are not used because there is no way to eliminate aminolysis at the wrong carbonyl of the anhydride. Acyl azides (see Section 2.13) are too laborious to make and too slow to react. The preparation of acyl chlorides (see Section 2.14) is too complicated for their routine use this may be rectified, however, by the availability of triphosgene (see Section 7.13). That leaves the following choices, bearing in mind that a two to three times molar excess of protected amino acid is always employed. 

F Albericio, LA Carpino. Coupling reagents and activation. Methods Enzymol. 289, 104—126, 1997. 

The advent of numerous new coupling reagents and the drawbacks discussed below have substantially decreased the popularity of mixed anhydrides for peptide synthesis in the laboratory. The mixed anhydride method is, therefore, a frequently overlooked technique which is an effective tool for peptide synthesis. This procedure has been comprehensively reviewed and, as stated by Meienhofer, the mixed anhydride method, when carried out under well-defined reaction conditions, is considerably less afflicted with undesired side reactions than, for example, the azide or carbodiimide procedures. 

FIGURE 3.14 Schematic representation of (a) Curtis azide activation and (b) coupling reagents activation method. 

Fig. 16. Schematic presentation ofpeptide synthesis by inverse solid phase method based on the use of polymer-bound amino acid active esters (coupling reagent) and polymer-bound jnperazine (deprotecting reagent)...

Alberico F, Carpino LA. Coupling reagents and activation. In Fields GB, ed. Solid-Phase Peptide Synthesis. Methods in Enzymology, vol 289. New York Academic Press,... 

Recent interest in the synthesis of oligopeptides has led to the development of many methods of amide preparation. The search for new coupling reagents and effective activation processes remains a major area of interest, and away from the peptide area syntheses of unsaturated and oxygenated amides are actively pursued. Benzo-... 

Preparation.—Modifications of the standard procedure (R COjH + R SH) employ 4-(dimethylamino)pyridine and dicyclohexylcarbodi-imide, diphenylphosphinyl chloride, or Me2NP(0)Cl2 as coupling reagents. Related methods e,g. acyl... 

Albericio, F. Carpino, L. A. Coupling reagents and activation. Method. Enzymol., 1997,289,104—126. 

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