Peptide Coupling Reagents

Coupling reagents activate a carboxylic acid toward a free amine, forming the amide (peptide) bond that joins amino-acid residues. They are the workhorses of solid-phase peptide synthesis (SPPS) and solution-phase peptide chemistry: the reagent converts the acid into a reactive active ester or acyloxyphosphonium species that acylates the incoming amine under mild conditions, while its design controls coupling rate and suppresses racemisation at the α-carbon.

This collection spans the principal reagent families used in modern peptide and amide-bond formation — the aminium/uronium salts such as HBTU, HCTU and TBTU; the phosphonium salts such as PyBOP, PyAOP and the Oxyma-based PyOxim; the morpholino-based COMU; the carbodiimides and active-ester additives; and acyl-transfer catalysts such as DMAP that complete the toolkit. Every listing carries verified identifiers, structural detail, and the practical handling notes a synthetic chemist needs to match a reagent to the coupling at hand.

For help choosing between these classes, see NorrChemica's Lab Journal guide: Choosing a Coupling Reagent for Amide and Peptide Bond Formation.