Liposome-Assisted Selective Polycondensation of α-Amino Acids and Peptides:  the Case of Charged Liposomes

Successive addition of N-carboxyanhydride (NCA) Trp to POPC liposomes showed that multiple feeding permits the formation of much longer Trp-oligomers compared to the reference system with no liposomes. Mixed POPC/DDAB liposomes were used to obtain block co-oligopeptides containing both Trp and Glu residues in the same chain. By using the lipophilic condensing agent EEDQ in the absence and presence of POPC liposomes, significant amounts of oligo-Trps were obtained only for the latter case. EEDQ-induced condensation in the presence of POPC liposomes and a library of four dipeptides, H−TrpTrp−OH, H−TrpGly−OH, H−TrpAsp−OH, and H−TrpGlu−OH, led to the selective formation of hydrophobic Trp-oligomers, since H−TrpTrp−OH is the only dipeptide out of the pool that exhibits affinity for the POPC membrane. Oligomers of H−ArgTrp−OH or H−HisTrp−OH were obtained only in significant yields in the presence of negatively charged POPC/DOPA liposomes. The case of the synthesis of H−HisTrpHisTrp−OH is shown as an example of in situ preparation of a reactive, potentially catalytically active compound.