Reduced pulmonary surfactant interaction of daptomycin analogs via tryptophan replacement with alternative amino acids

Yong He; Jing Li; Nin Yin; Prudencio S Herradura; Larry Martel; Yanzhi Zhang; Andre L Pearson; Vidya Kulkarni; Carmela Mascio; Karen Howland; Jared A Silverman; Dennis D Keith; Chester A Metcalf

doi:10.1016/j.bmcl.2012.08.013

Reduced pulmonary surfactant interaction of daptomycin analogs via tryptophan replacement with alternative amino acids

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6248-51. doi: 10.1016/j.bmcl.2012.08.013. Epub 2012 Aug 9.

Authors

Yong He¹, Jing Li, Nin Yin, Prudencio S Herradura, Larry Martel, Yanzhi Zhang, Andre L Pearson, Vidya Kulkarni, Carmela Mascio, Karen Howland, Jared A Silverman, Dennis D Keith, Chester A Metcalf

Affiliation

¹ Cubist Pharmaceuticals, 65 Hyden Ave, Lexington, MA 02421, United States. yong.he@cubist.com

PMID: 22951041
DOI: 10.1016/j.bmcl.2012.08.013

Abstract

Daptomycin was shown to interact in vitro with pulmonary surfactant leading to reduction of its antibacterial activity. We report herein the preparation and anti-staphylococcal activity of a series of daptomycin analogs with reduced pulmonary surfactant interaction by replacing tryptophan with various amino acids.

MeSH terms

Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Daptomycin / analogs & derivatives*
Daptomycin / chemistry
Daptomycin / pharmacology*
Microbial Sensitivity Tests
Molecular Conformation
Pulmonary Surfactants / chemistry*
Staphylococcus aureus / drug effects*
Tryptophan / metabolism*

Substances

Anti-Bacterial Agents
Pulmonary Surfactants
Tryptophan
Daptomycin