Synthesis of six-membered carbocyclic ring α,α-disubstituted amino acids and arginine-rich peptides to investigate the effect of ring size on the properties of the peptide

Cell-penetrating peptides (CPPs) have been attracting attention as tools for intracellular delivery of membrane-impermeant functional molecules. Among the variety CPPs that developed, many are composed both natural and unnatural amino acids. We previously synthesized α,α-disubstituted α-amino acids (dAAs) containing a five-membered carbocyclic ring in its side chain revealed utility dAAs development novel CPPs. In present study, we designed six-membered dAA with an group on introduced it into arginine (Arg)-rich to further investigate value developing also assessed effects size cellular uptake dAA-containing peptides. The stability peptide's secondary structure membrane permeability were greater than Arg nonapeptide. However, number carbon atoms had little effect. Nevertheless, these results show cyclic design