title: Structure-activity relationship of daptomycin analogues with substitution at (2S, 3R) 3-methyl glutamic acid position.
abstract: Daptomycin is a highly effective lipopeptide antibiotic against Gram-positive pathogens. The presence of (2S, 3R) 3-methyl glutamic acid (mGlu) in daptomycin has been found to be important to the antibacterial activity. However the role of (2S, 3R) mGlu is yet to be revealed. Herein, we reported the syntheses of three daptomycin analogues with (2S, 3R) mGlu substituted by (2S, 3R) methyl glutamine (mGln), dimethyl glutamic acid and (2S, 3R) ethyl glutamic acid (eGlu), respectively, and their antibacterial activities. The detailed synthesis of dimethyl glutamic acid was also reported.
authors.affiliation: Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Du'an
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Hiu Yung
authors.initials: HY
authors.lastname: Lam
authors.affiliation: Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong Special Administrative Region.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Han
authors.affiliation: Cubist Pharmaceutical, Inc., 65 Hayden Avenue, Lexington, MA 02421, United States.
authors.forename: Nicole
authors.initials: N
authors.lastname: Cotroneo
authors.affiliation: Cubist Pharmaceutical, Inc., 65 Hayden Avenue, Lexington, MA 02421, United States. Electronic address: pandya.bhaumik@gmail.com.
authors.forename: Bhaumik A
authors.initials: BA
authors.lastname: Pandya
authors.affiliation: Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address: xuechenl@hku.hk.
authors.forename: Xuechen
authors.initials: X
authors.lastname: Li
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017576:Daptomycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D018698:Glutamic Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D018698:Glutamic Acid; D017576:Daptomycin
keywords: Antibiotics; Daptomycin; Methyl glutamic acid; Solid phase peptide synthesis; Structure-activity relationship