Synthesis of chemotactic peptides.

TLDR: This chapter discusses the synthesis of the prototype peptide N α formyl-Met-Leu-Phe-OH (fMLP), a series of repetitive deprotections of t-Boc-amino acids or peptides using trifluoroacetic acid (TFA), subsequent neutralization with N-methyl morpholine (NMM), followed by coupling of the next t-Bsino acid using a rapid mixed anhydride method.

Abstract: Publisher Summary This chapter discusses the synthesis of the prototype peptide N α formyl-Met-Leu-Phe-OH (fMLP). The steps are a series of repetitive deprotections of t-Boc-amino acids or peptides using trifluoroacetic acid (TFA), subsequent neutralization with N-methyl morpholine (NMM), followed by coupling of the next t-Boc-amino acid using a rapid mixed anhydride method. Although several methods are available for the formylation of peptides, consistently excellent results have been obtained using the anhydride of isovaleryl chloride and formic acid. The same general protocol is used for the synthesis of the antagonists. The prototype analog is the pentapeptide, t-Boc-Phe-Leu-Phe-Leu-Phe-OH. The final step, however, is a catalytic hydrogenolysis to yield the t-Boc-free acid form of the desired peptide. Although the synthesis for the pentapeptide is presented, the tripeptide t-Boc-Phe-Leu-Phe-OH is also fully active and only slightly less potent. No solid-phase synthesis for the antagonists has been reported.