Tetrahydropyranyl Backbone Protection for Enhanced Fmoc Solid-Phase Peptide Synthesis

Abstract

Fmoc solid-phase peptide synthesis has been indispensable for the efficient manufacture of research grade peptides and proteins, and peptide APIs. However, the solid-phase approach is still hampered by solubility issues and aggregation of the resin-bound peptide chain, which limits routine access to peptides > 40 amino acids in length. The use of backbone amide protecting groups, such as through the introduction of N-benzyl-based moieties and pseudoproline dipeptides, ameliorates this synthetic inefficiency somewhat. But benzyl groups can be difficult to remove postassembly, and pseudoprolines are limited to serine, threonine, and cysteine-rich peptide segments. To enhance the utility of bac..