Article
Rational design of balanced dual-targeting antibiotics with limited resistance.
PLoS biology - 1 Oct 2020
Nyerges Akos, Tomašič Tihomir, Durcik Martina, Revesz Tamas, Szili Petra, Draskovits Gabor, Bogar Ferenc, Skok Žiga, Zidar Nace, Ilaš Janez, Zega Anamarija, Kikelj Danijel, Daruka Lejla, Kintses Balint, Vasarhelyi Balint, Foldesi Imre, Kata Diána, Welin Martin, Kimbung Raymond, Focht Dorota, Mašič Lucija Peterlin, Pal Csaba
Abstract excerpt
Antibiotics that inhibit multiple bacterial targets offer a promising therapeutic strategy against resistance evolution, but developing such antibiotics is challenging. Here we demonstrate that a rational design of balanced multitargeting antibiotics is feasible by using a medicinal chemistry workflow. The resultant lead compounds, ULD1 and ULD2, belonging to a novel chemical class, almost equipotently inhibit...
Topics
- Amino Acid Sequence
- Animals
- Anti-Bacterial Agents
- Bacterial Proteins
- Directed Molecular Evolution
- Disease Models, Animal
- Drug Design
- Drug Resistance, Multiple, Bacterial
- Enzyme Inhibitors