Plenary Talk: Glycosylated cationic block poly(?-peptides) for potentiating antibiotics against Gram-negative bacteria

Zhangyong Si¹, Yu Du¹, Moon¹, Damien¹, Jothy¹, Yang Liu², Kaixi Zhang¹, Sheethal¹, Chun Kiat Yeo¹, Yuguang Mu², Kevin Pethe³, MB Chan-Park¹*

1. Centre for Antimicrobial Bioengineering, School of Chemical and Biomedical Engineering, NTU, 62 Nanyang Drive, Singapore 637459, Singapore.
2. School of Biological Sciences, NTU
3. Lee Kong Chian School of Medicine, NTU

The rise of multi-drug resistant (MDR) bacteria together with the decrease of useful antibiotics has been a mounting problem. Especially for Gram-negative bacteria, no new family of drug was found in the last past 50 years. Herein, we developed a novel glyco-β-peptides through one-step polymerization, following by one-pot global deprotection to get water soluble polymers. Our glyco-β-peptides had relatively good antimicrobial activity against both Gram-negative P. aeruginosa and Gram-postive S.aureaus, with MIC of 64 µg/mL. In vivo biocompatibility test using a murine intravenous toxicity model at dosage of 10 mg/kg indicated that glycopeptide had excellent biocompatibility, with 100% animal survival after 7 days and no significant difference in all the clinical important biomarker compared to the control groups. Our polymer could work synergistically with antibiotics at low concentration (16µg/mL), to potentiate conventional traditional antibiotic against wide type P.aeruginosa and their clinical relevant strain PAN-sensitive (PAES), clinical isolate P. aeruginosa D25, P. aeruginosa D1 and clinical multi-drug resistant strain PAER (almost no antibiotic showed effect except colistn) greater than 16 times.