Display options
Share it on

Antibiotics (Basel). 2017 Sep 11;6(3). doi: 10.3390/antibiotics6030018.

Synthesis and Immunological Evaluation of Virus-Like Particle-Milbemycin A₃/A₄ Conjugates.

Antibiotics (Basel, Switzerland)

Andris Zeltins, Māris Turks, Dace Skrastina, Jevgeņija Lugiņina, Ieva Kalnciema, Ina Balke, Ērika Bizdēna, Vitalijs Skrivelis

Affiliations

  1. Latvian Biomedical Research and Study Centre, Ratsupites 1, LV-1067 Riga, Latvia. [email protected].
  2. Institute of Technology of Organic Chemistry, Riga Technical University, P. Valdena Str. 3, LV-1048 Riga, Latvia. [email protected].
  3. Latvian Biomedical Research and Study Centre, Ratsupites 1, LV-1067 Riga, Latvia. [email protected].
  4. Institute of Technology of Organic Chemistry, Riga Technical University, P. Valdena Str. 3, LV-1048 Riga, Latvia. [email protected].
  5. Latvian Biomedical Research and Study Centre, Ratsupites 1, LV-1067 Riga, Latvia. [email protected].
  6. Latvian Biomedical Research and Study Centre, Ratsupites 1, LV-1067 Riga, Latvia.
  7. Institute of Technology of Organic Chemistry, Riga Technical University, P. Valdena Str. 3, LV-1048 Riga, Latvia. [email protected].
  8. PharmIdea Ltd., Rupnicu 4, Olaine, Riga District, LV-2114 Olaine, Latvia. [email protected].

PMID: 28892001 PMCID: PMC5617982 DOI: 10.3390/antibiotics6030018

Abstract

Milbemycins are macrolide antibiotics with a broad spectrum of nematocidal, insecticidal, and acaricidal activity. To obtain milbemycin A₃/A₄ derivatives suitable for chemical conjugation to protein carriers (milbemycin haptens), succinate linker and a novel 17-atom-long linker containing a terminal carboxylic acid group were attached to the milbemycin core in a protecting group-free synthesis. The obtained milbemycin A₃/A₄ derivatives were coupled to Potato virus Y-like nanoparticles by the activated ester method. The reaction products were characterized and used in mice immunization experiments. It was found that the mice developed weak specific immune responses toward all tested milbemycin haptens.

Keywords: ELISA; hydrophobic hapten; macrocyclic lactone; plant virus

Conflict of interest statement

The authors declare no conflict of interest. The funder of the study had no role in study design, data analysis and interpretation, or writing of the article.

References

  1. Nat Prod Res. 2013 Oct;27(20):1936-9 - PubMed
  2. Antimicrob Agents Chemother. 1991 Sep;35(9):1811-7 - PubMed
  3. Anal Bioanal Chem. 2012 Nov;404(8):2203-22 - PubMed
  4. Microb Cell Fact. 2017 Jan 17;16(1):9 - PubMed
  5. Hybridoma. 1996 Feb;15(1):1-9 - PubMed
  6. Mol Biotechnol. 2012 Oct;52(2):129-39 - PubMed
  7. Biotechnol Adv. 2007 Jul-Aug;25(4):333-52 - PubMed
  8. J Immunol Methods. 2010 Aug 31;360(1-2):103-18 - PubMed
  9. Antimicrob Agents Chemother. 2013 Feb;57(2):1040-6 - PubMed
  10. Curr Pharm Biotechnol. 2012 May;13(6):936-51 - PubMed
  11. Molecules. 2012 Jun 15;17(6):7401-14 - PubMed
  12. Nat Chem. 2015 Dec;7(12):952-60 - PubMed
  13. J Med Chem. 1982 Jun;25(6):658-63 - PubMed
  14. J Antibiot (Tokyo). 1983 May;36(5):509-15 - PubMed
  15. J Chromatogr A. 2016 Nov 4;1471:118-125 - PubMed
  16. PLoS One. 2015 Jul 27;10(7):e0134042 - PubMed

Publication Types