Novltex: A New Class of Antibiotics with Potent Activity against Multidrug-Resistant Bacterial Pathogens─Design, Synthesis, and Biological Evaluation.

ABSTRACT: Increasing spread of multidrug-resistant (MDR) bacteria demands antibiotics that combine potent activity with scalable synthesis. Novo29 (clovibactin) is promising but suffers from low yield (1%), dependence on costly and noncommercial d-hydroxy-asparagine (d-Hyn₅), and lengthy syntheses. We report "Novltex", a novel class of antibiotic that fuses the Leu₁₀-teixobactin macrocycle to the Novo29 N-terminus tail, replacing d-Hyn₅ with inexpensive threonine. Our efficient synthesis delivers 30% yield with faster coupling cycles (∼10 min), enabling rapid and low-cost scale-up. A 16-member analogue library systematically probing amino-acid configuration identified analogue 4 (d-Leu₂) as the initial lead, informing the rational design of analogue

SUBMITTER: Malkawi E 

PROVIDER: S-EPMC12481569 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature