Pharmacology and Therapeutics - Research Publications

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The impact of backbone N-methylation on the structure-activity relationship of Leu₁₀-teixobactin

Velkov, T ; Swarbrick, JD ; Hussein, MH ; Schneider-Futschik, EK ; Hoyer, D ; Li, J ; Karas, JA (WILEY, 2019-09)

Antimicrobial resistance is a serious threat to global human health; therefore, new anti-infective therapeutics are required. The cyclic depsi-peptide teixobactin exhibits potent antimicrobial activity against several Gram-positive pathogens. To study the natural product's mechanism of action and improve its pharmacological properties, efficient chemical methods for preparing teixobactin analogues are required to expedite structure-activity relationship studies. Described herein is a synthetic route that enables rapid access to analogues. Furthermore, our new N-methylated analogues highlight that hydrogen bonding along the N-terminal tail is likely to be important for antimicrobial activity.