Hydrophilic Modifications of an Amphiphilic Polynorbornene and the Effects on its Hemolytic and Antibacterial Activity

Abstract

Here, we report the modification of an amphiphilic antibacterial polynorbornene, Poly3, via incorporation of hydrophilic, biocompatible groups. The sugar, zwitterionic, and polyethylene glycol based moieties were incorporated in varying ratios by copolymerization and post-polymerization techniques. Well-defined copolymers with molecular weights of 3 kDa and narrow polydispersity indices from 1.08 to 1.15 were obtained. The effects of these modifications on the biological activity of these polymers were analyzed by determining their minimum inhibitory concentrations (MIC) and their hemolytic activities (HC50).

Helical antimicrobial polypeptides with radial amphiphilicity

“…Discounting the two terminal residues to eliminate end effects, the peptide backbone is close to the ideal helix, RMSD helix = (0.04 ± 0.01) nm, with a radius r helix = (0.232 ± 0.002) nm and twist γ helix = (100 ± 1)°a lso nearly ideal (r ideal helix = 0.23 nm, γ ideal helix = 100°). The mean per residue molar ellipticity at 222 nm computed from our simulations using Dichro-Calc (comp.chem.nottingham.ac.uk/ cgi-bin/dichrocalc/bin/getparams.cgi) (47) of [θ] 222 nm = (−21 ± 1) × 10 3 degrees (deg) cm 2 /dmol is in excellent agreement with the experimental value of −23 × 10 3 deg cm 2 /dmol for PHLGBIm 40 and −19 × 10 3 deg cm 2 /dmol for PHLG-BIm 28 reported in Fig. 1D.…”

“…1E). The helical PHLGBIm 40 showed higher antibacterial activity than the nonhelical PHDLG-BIm 40 , with MIC values 16, 4, 4, and 4 times lower against DH5α, MG1655, ATCC12608, and ATCC11778, respectively. Length was also found to influence the antimicrobial activity of the RA polypeptides, as PHLG-BIm 28 , with DP of 28, showed lower antimicrobial activity compared with PHLGBIm 40 .…”

“…With an RA structure, PHLG-BIm 40 showed strong antibacterial activity against both gram-negative bacteria, DH5α and MG1655, and gram-positive bacteria, ATCC12608 and ATCC11778, with MIC values of 3.3, 26.1, 13.1, and 13.1 μM, respectively (Fig. 1E).…”

“…There has also been growing interest in synthetic polymer-based AMP mimics bearing both cationic and hydrophobic groups, which can be prepared through cost-effective polymerization processes. For example, simplified polymeric AMP analogs have been developed, including poly (methacrylamides) (31), poly(β-lactams) (14,(32)(33)(34)(35), polypeptides (36)(37)(38), poly(norborenes) (39,40), and poly(carbonates) (41,42). These compounds are considerably less expensive than peptides, and much work is being done to optimize them.…”

Antimicrobial Polymers: Mimicking Amino Acid Functionali ty, Sequence Control and Three-dimensional Structure of Host-defen se Peptides

“…Similar results were observed for poly(norbornene) copolymers when extended by either zwitterionic, sugar or PEG moieties. 31 In the case of polyacrylics, a complete exchange of the hydrophobic component (HEMA 32 or PEGMA 33 ) still results in antimicrobial polymers. However, it is unclear whether these systems still target the bacterial membrane like other AMP mimics.…”