An important feature that has enabled the broad application of SPPS is the generation of extremely high yields in the coupling step. Highly efficient amide bond-formation conditions are required. To illustrate the impact of suboptimal coupling yields for a given synthesis, consider the case where each coupling step were to have at least 99% yield: this would result in a 77% overall crude yield for a 26-amino acid peptide (assuming 100% yield in each deprotection); if each coupling were 95% efficient, the overall yield would be 25%. and adding an excess of each amino acid (between 2- and 10-fold). The minimization of amino acid racemization during coupling is also of vital importance to avoid epimerization in the final peptide product.
Amide bond formation between an amine and carboxylic acid is slow, and as such usually requires  coupling reagents or activators. A wide range of coupling reagents exist, due in part to their varying effectiveness for particular couplings, many of these reagents are commercially available.