Structure-Activity Relationships of Daptomycin Lipopeptides

John A. Karas, Glen P. Carter, Benjamin P. Howden, Adrianna M. Turner, Olivia K.A. Paulin, James D. Swarbrick, Mark A. Baker, Jian Li, Tony Velkov

Research output: Contribution to journalReview ArticleResearchpeer-review

35 Citations (Scopus)


Daptomycin is a calcium-dependent cyclic lipodepsipeptide derived from the soil saprotroph Streptomyces roseosporus, and its antibiotic properties make it a key agent for treatment of drug-resistant Gram-positive infections. It is most commonly used clinically for the treatment of Gram-positive skin and skin structure infections (SSSI), Staphylococcus aureus bacteremia, and right-sided endocarditis infections associated with S. aureus, including methicillin resistant S. aureus (MRSA). It has also been used "off-label"for Enterococcal infections. There has been a tremendous amount of research investigating its mode of action, resistance mechanisms, and biosynthesis of this clinically important antimicrobial agent. Although we cover the latter aspects in detail, the primary focus of this review is to provide the most comprehensive and up-to-date reference for the medicinal chemist on the structure-activity-toxicity of this important class of lipopeptide antibiotics.

Original languageEnglish
Pages (from-to)13266-13290
Number of pages25
JournalJournal of Medicinal Chemistry
Issue number22
Publication statusPublished - 25 Nov 2020

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