Daptomycin: Difference between revisions

{{Use dmy dates|date=SeptemberMarch 20192024}}

It has been proposed that the formation of spherical micelles<ref>{{cite journal | vauthors = Kirkham S, Castelletto V, Hamley IW, Inoue K, Rambo R, Reza M, Ruokolainen J | title = Self-Assembly of the Cyclic Lipopeptide Daptomycin: Spherical Micelle Formation Does Not Depend on the Presence of Calcium Chloride | journal = ChemPhysChem | volume = 17 | issue = 14 | pages = 2118–2122 | date = July 2016 | pmid = 27043447 | doi = 10.1002/cphc.201600308 | s2cid = 44681934 | url = https://centaur.reading.ac.uk/66618/3/02.09.2016%20IWH%20DaptomycinAngewChem.pdf }}</ref> by daptomycin may affect the mode of action.

In Phase III clinical trials, limited data showed daptomycin to be associated with poor outcomes in patients with left-sided endocarditis.{{Citation needed|date=September 2012}} Daptomycin has not been studied in patients with [[prosthetic heart valve|prosthetic valve]] endocarditis or meningitis.<ref name=Cubist2005>{{cite web | url = http://cubicin.com/ | title = Cubicin (daptomycin for injection) | publisher = Cubist Pharmaceuticals | access-date = 17 March 2018 | archive-date = 11 April 2021 | archive-url = https://web.archive.org/web/20210411015507/https://www.cubicin.com/ | url-status = dead }}</ref>

Daptomycin is a cyclic lipopeptide antibiotic produced by ''[[Streptomyces roseosporusfilamentosus]]''.<ref>{{cite journal | vauthors = Miao V, Coëffet-LeGal MF, Brian P, Brost R, Penn J, Whiting A, Martin S, Ford R, Parr I, Bouchard M, Silva CJ, Wrigley SK, Baltz RH | display-authors = 6 | title = Daptomycin biosynthesis in Streptomyces roseosporus: cloning and analysis of the gene cluster and revision of peptide stereochemistry | journal = Microbiology | volume = 151 | issue = Pt 5 | pages = 1507–1523 | date = May 2005 | pmid = 15870461 | doi = 10.1099/mic.0.27757-0 | doi-access = free }}</ref><ref name=Steenbergen>{{cite journal | vauthors = Steenbergen JN, Alder J, Thorne GM, Tally FP | title = Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections | journal = The Journal of Antimicrobial Chemotherapy | volume = 55 | issue = 3 | pages = 283–288 | date = March 2005 | pmid = 15705644 | doi = 10.1093/jac/dkh546 | doi-access = free }}</ref> Daptomycin consists of 13 amino acids, 10 of which are arranged in a cyclic fashion, and three on an exocyclic tail. Two nonproteinogenic amino acids exist in the drug, the unusual amino acid [[L-kynurenine]] (Kyn), only known to daptomycin, and L-3-methylglutamic acid (mGlu). The N-terminus of the exocyclic tryptophan residue is coupled to decanoic acid, a medium-chain (C10) fatty acid. Biosynthesis is initiated by the coupling of decanoic acid to the N-terminal [[tryptophan]], followed by the coupling of the remaining amino acids by nonribosomal peptide synthetase (NRPS) mechanisms. Finally, a cyclization event occurs, which is catalyzed by a thioesterase enzyme, and subsequent release of the lipopeptide is granted. {{cn|date=February 2023}}

''Streptomyces roseosporus'', the producer organism of daptomycin, is amenable to genetic manipulation;<ref name=Baltz16193281>{{cite journal | vauthors = Baltz RH, Brian P, Miao V, Wrigley SK | title = Combinatorial biosynthesis of lipopeptide antibiotics in Streptomyces roseosporus | journal = Journal of Industrial Microbiology & Biotechnology | volume = 33 | issue = 2 | pages = 66–74 | date = February 2006 | pmid = 16193281 | doi = 10.1007/s10295-005-0030-y | s2cid = 10856890 | doi-access = free }}</ref> the daptomycin biosynthetic gene cluster has been cloned, sequenced, and expressed in ''S. lividans'';<ref name=Baltz16311632/> the lipopeptide biosynthetic machinery has the potential to be interrupted by variations of natural precursors, as well as precursor-directed biosynthesis, gene deletion, genetic exchange, and module exchange;<ref name=Baltz16193281/> the molecular engineering tools have been developed to facilitate the expression of the three individual NRPS genes from three different sites in the chromosome, using ermEp* for expression of two genes from ectopic loci;<ref>{{cite journal | vauthors = Nguyen KT, Ritz D, Gu JQ, Alexander D, Chu M, Miao V, Brian P, Baltz RH | display-authors = 6 | title = Combinatorial biosynthesis of novel antibiotics related to daptomycin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 46 | pages = 17462–17467 | date = November 2006 | pmid = 17090667 | pmc = 1859951 | doi = 10.1073/pnas.0608589103 | doi-access = free | bibcode = 2006PNAS..10317462N }}</ref> other lipopeptide gene clusters, both related and unrelated to daptomycin, have been cloned and sequenced,<ref name=Nguyen/> thus providing genes and modules to allow the generation of hybrid molecules;<ref name=Baltz16193281/> derivatives can be afforded via chemoenzymatic synthesis;<ref>{{cite journal | vauthors = Kopp F, Grünewald J, Mahlert C, Marahiel MA | title = Chemoenzymatic design of acidic lipopeptide hybrids: new insights into the structure-activity relationship of daptomycin and A54145 | journal = Biochemistry | volume = 45 | issue = 35 | pages = 10474–10481 | date = September 2006 | pmid = 16939199 | doi = 10.1021/bi0609422 }}</ref> and lastly, efforts in medicinal chemistry are able to further modify these products of molecular engineering.<ref name=Baltz16311632/>

Daptomycin, originally designated as LY 146032, was discovered by researchers at [[Eli Lilly and Company]] in the late 1980s from the [[actinomycete]] ''[[Streptomyces roseosporus]]''. LY 146032 showed promise in phase I/II [[clinical trial]]s for treatment of infection caused by Gram-positive organisms. Lilly ceased development because high-dose therapy was associated with adverse effects on skeletal muscle, including [[myalgia]].<ref>{{cite journal | vauthors = Eisenstein BI, Oleson FB, Baltz RH | title = Daptomycin: from the mountain to the clinic, with essential help from Francis Tally, MD | journal = Clinical Infectious Diseases | volume = 50 | issue = Supplement_1 | pages = S10–S15 | date = January 2010 | pmid = 20067387 | doi = 10.1086/647938 | publication-date = 1 February 2010-02-01 | doi-access = free }}</ref><ref name=Tally2000>{{cite journal | vauthors = Tally FP, DeBruin MF | title = Development of daptomycin for gram-positive infections | journal = The Journal of Antimicrobial Chemotherapy | volume = 46 | issue = 4 | pages = 523–526 | date = October 2000 | pmid = 11020247 | doi = 10.1093/jac/46.4.523 | doi-access = free }}</ref>

The rights to LY 146032 were acquired by [[Cubist Pharmaceuticals]] in 1997, which following U.S. [[Food and Drug Administration]] (FDA) approval in September 2003, for use in people older than 18 years, began marketing the drug under the trade name Cubicin. Cubicin is marketed in the EU and in several other countries by [[Novartis]] following its purchase of [[Chiron Corporation]], the previous licensee.<ref name="Tally2000" /><ref name="Charles 2004">{{cite journal | vauthors = Charles PG, Grayson ML | title = The dearth of new antibiotic development: why we should be worried and what we can do about it | journal = The Medical Journal of Australia | volume = 181 | issue = 10 | pages = 549–553 | date = November 2004 | pmid = 15540967 | doi = 10.5694/j.1326-5377.2004.tb06444.x | s2cid = 18526863 }}</ref>

* {{cite journal | vauthors = Pirri G, Giuliani A, Nicoletto S, Pizutto L, Rinaldi A |title=Lipopeptides as anti-infectives: a practical perspective |journal=Cent. Eur. J. Biol. |volume=4 |issue=3 |pages=258–273 |year=2009 |doi=10.2478/s11535-009-0031-3|doi-access=free |url=https://www.openaccessrepository.it/record/118487/files/fulltext.pdf }}

[[Category:Drugs developed by Eli Lilly and Company brands]]

[[Category:AstraZenecaDrugs brandsdeveloped by AstraZeneca]]

[[Category:Drugs developed by Merck & Co. brands]]