Narrowing down chain length effects on the antibacterial action of guanylated oligomers

Synthesis of monodisperse guanylated oligomers through reversible addition fragmentation chain transfer (RAFT) polymerization of 2-Boc aminoethyl acrylate followed by flash chromatography is described. To achieve antimicrobial action, the RAFT-derived protected amine polymer was first separated into its oligomer constituents, followed by removal of the RAFT chain end, introduction of a C-12 hydrophobic tail via thiol-ene conjugation, and guanylation. Oligomers with increasing discrete chain length were tested for their antimicrobial activity. Chain lengths below 6 were shown to be less effective towards Gram positive bacteria in MIC assays compared to higher chain lengths, in line with literature that indicates a required minimum chain length for activity for similar compounds. Comparing the activity of chain length 6, 7 and 8 suggests that chain length 6 is indeed the most active compound. Identification of the ideal chain length for antimicrobial action enables future production of more selective antimicrobial peptide mimics, since polydisperse materials (as tested previously) show significant variation of chain lengths around the mean average.