Carbodiimide coupling carboxylate-modified

A novel approach to peptide synthesis has been the use of a chloromethylated polystyrene polymer as an insoluble but porous solid phase on which the coupling reactions are carried out. Attachment to the polymer, constitutes protection of the carboxyl group (as a modified benzyl ester), and the peptide is lengthened from its amino-end by successive carbodiimide couplings. The method has been applied to the synthesis of a tetrapeptide, but incomplete reactions lead to the accumulation of by products. Further development of this interesting method is awaited. 

Hydrazide-containing compounds also can be coupled to carboxylate groups using a carbodiimide-mediated reaction. Using bifunctional hydrazide reagents, carboxylates can be modified to possess terminal hydrazide groups able to conjugate with other carbonyl compounds (Chapter 4, Section 8). 

These Ru(H)bpy32+ fluorescent silica nanoparticles were used to detect single bacterial cells using antibodies conjugated to the surface after functionalization with trimethoxysilyl-propyldiethylenetriamine followed by succinylation to create carboxylates. Specific antibody molecules against E. coli 0157 then were coupled to this modified fluorescent particle using the carbodiimide method with EDC and NHS (Zhao et al., 2004). 

The ethylene diamine-dextran derivative may be used for the coupling of carboxylate-contain-ing molecules by the carbodiimide reaction, for the coupling of amine-reactive probes, or to modify further using heterobifunctional crosslinkers. The hydrazide-dextran derivative may be used to crosslink aldehyde-containing molecules, such as oxidized carbohydrates or glycoproteins. 

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