Using Diphenylphosphoryl Azide (DPPA) for the Facile Synthesis of Biodegradable Antiseptic Random Copolypeptides

Yuji Pu, Yu Du, Mya Mya Khin, Vikashini Ravikumar, Scott A. Rice, Hongwei Duan*, Mary B. Chan-Park

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

A facile method has been developed for the large-scale synthesis of random copolypeptides composed of multiple (i.e., cationic, hydrophobic, and hydrophilic) amino acids and their relative ratios have been optimized for broad-spectrum antibacterial effect. The copolypeptides obtained have measured compositions close to the design ratios in spite of the differing reactivities of the different amino acids. An optimized random copolypeptide of lysine, leucine, and serine (denoted as KLS-3) mimicking the composition of LL-37 host defense peptide gives broad spectrum antibacterial activity against clinically relevant Gram-negative and Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAO1) with minimum inhibitory concentrations (MICs) of 32–64 μg mL−1, as well as good MICs against multidrug resistant Gram-negative bacteria of Escherichia coli EC 958 (64 μg mL−1) and Klebseilla pneumoniae PTR3 (128 μg mL−1). This method can be applied to the facile large-scale copolymerization of multiple amino acids, including unnatural amino acids, to make effective antibacterial copolypeptides. (Figure presented.).

Original languageEnglish
Article number1600601
JournalMacromolecular Rapid Communications
Volume38
Issue number7
DOIs
Publication statusPublished - Apr 1 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

ASJC Scopus Subject Areas

  • Polymers and Plastics
  • Organic Chemistry
  • Materials Chemistry

Keywords

  • antibacterial peptides
  • broad-spectrum antibacterial activity
  • diphenylphosphoryl azide
  • peptide synthesis

Fingerprint

Dive into the research topics of 'Using Diphenylphosphoryl Azide (DPPA) for the Facile Synthesis of Biodegradable Antiseptic Random Copolypeptides'. Together they form a unique fingerprint.

Cite this