Researchers: Christine M. Artim, Javon Walker, and Meghan K. O'Leary
The emergence of antibiotic resistance is a significant threat to human health, yet new antibiotic development has been unable to keep pace with emergence of resistant bacteria. To combat this issue, the Alabi lab is investigating the oligoTEA scaffold as a platform for development of antibacterial agents. Recently, a library of oligoTEAs made with amino N-allyl-acrylamide monomers demonstrated antibacterial activity against MRSA, B. subtilis, VRE, and S. epidermidis. The structure, hydrophobicity, and charge of oligoTEAs can be easily tailored to yield compounds with antibacterial activity at low micromolar concentrations yet very low mammalian cell toxicity. These synthetic peptide mimetics operate via membrane permeabilization, similar to natural antimicrobial peptides. However, unlike AMPs, AOTs have an abiotic backbone that is unsusceptible to proteolysis, and maintain their activity in the presence of serum. These traits suggest that AOTs could be promising candidates for development of new, potent antibiotics.
Artim CM,Phan NN, and Alabi CA. Effect of Composition on Antibacterial Activity of Sequence-Defined Cationic OligoTEAs. ACS Infect. Dis. 2018. DOI: 10.1021/acsinfecdis.8b00079
Porel M, Thornlow DN, Artim CM, and Alabi CA. Sequence-Defined Backbone Modifications Regulate Antibacterial Activity of OligoTEAs. ACS Chem. Bio. 2017. DOI: 10.1021/acschembio.6b00837
Porel M, Thornlow DN, Phan NN and Alabi CA. Sequence-defined Bioactive Macrocycles via an Acid-catalysed Cascade Reaction, Nature Chemistry 2016. DOI: 10.1038/nchem.2508