Synthesis of folate lipoconjugates with hydrophobic spacers
Abstract
Folate lipoconjugates were synthesized by induction of spacers to 1,2-di-O-tetradecyl-rac-glycerol for future condensation with folic acid. The intermediates hydrophobic compounds were obtained by treatment of 1-О-(4- nitrophenyloxycarbonyl)-2,3-di-O-tetradecyl-rac-glycerol with free diamines (1,4-diaminobutane, 1,6-diaminohexane, 1,8-diaminooctane, 1,12-diaminododecane) in the presence of triethylamine. Condensation of intermediate compounds (1 eq.) and folic acid (3 eq.) were carried out in the presence of (O-(benzotriazol-1-yl)- 1,1,3,3-tetramethyluronium tetrafluoroborate (3 eq.) and N,N-diisopropylethylamine (5 eq.) and gave targeted folate lipoconjugates. The structures and purity of the compounds synthesized were confirmed by analytic physicochemical methods.
About the Authors
E. V. Shmendel
M.V. Lomonosov Moscow State University of Fine Chemical Technologies, 86, Vernadskogo pr., Moscow 119571
Russian Federation
Russian Federation
S. V. Eremin
M.V. Lomonosov Moscow State University of Fine Chemical Technologies, 86, Vernadskogo pr., Moscow 119571
Russian Federation
Russian Federation
N. G. Morozova
Московский государственный университет тонких химических технологий им. М.В. Ломоносова
Russian Federation
Russian Federation
M. A. Maslov
M.V. Lomonosov Moscow State University of Fine Chemical Technologies, 86, Vernadskogo pr., Moscow 119571
Russian Federation
Russian Federation
References
1. Jun Wu, Qing Liu, Robert J. Lee. A folate receptor-targeted liposomal formulation for paclitaxel // Int. J. Pharmaceutics. 2006. V. 316. P. 148–153.
2. Faneca H., Cardoso A.L., Trabulo S., Duarte S., Pedroso de Lima M.C. Cationic liposome-based systems for nucleic acid delivery: from the formulation development to therapeutic applications / Drug Delivery Systems: Advanced Technologies Potentially Applicable in Personalised Treatment / Ed. Jorge Coelho. 2013. V. 4. P. 153–184.
3. Zhu C., Jung S., Luo S., Meng F., Zhu X., Park T.G., Zhong Z. Co-delivery of siRNA and paclitaxel into cancer cells by biodegradable cationic micelles based on PDMAEMA-PCL-PDMAEMA triblock copolymers // Biomaterials. 2010. V. 31. P. 2408–2416.
4. Maeda H. The enhanced permeability and retention (EPR) effect in tumor vasculature: The key role of tumor-selective macromolecular drug targeting // Adv. Enzyme Regul. 2001. V. 41. P. 189–207.
5. Xiang G., Wu J., Lu Y., Liu Z., Lee R.J. Synthesis and evaluation of a novel ligand for folate-mediated targeting liposomes // Int. J. Pharmaceutics. 2008. P. 29–36.
6. Chen S., Zhao X., Chen J., Chen J., Kuznetsova L., Wong S.S., Ojima I. Mechanism-based tumor-targeting drug delivery system. validation of efficient vitamin receptor-mediated endocytosis and drug release // Bioconjug. Chem. 2010. V. 21(5). P. 979–987.
7. Saeed A.O., Magnusson J.P., Moradi E., Soliman M., Wang W., Stolnik S., Thurecht K.J., Howdle S.M., Alexander C. Modular construction of multifunctional bioresponsive cell-targeted nanoparticles for gene delivery // Bioconjug. Chem. 2011. V. 22. P. 156–168.
8. Xia W., Low P.S. Folate-targeted therapies for cancer // J. Med. Chem. 2010. V. 53. P. 6811–6824.
9. Kamaly N., Kalber T., Thanou M., Bell J.D., Miller A.D. Folate receptor targeted bimodal liposomes for tumor magnetic resonance imaging // Bioconjug. Chem. 2009. V. 20. P. 648–655.
10. Шмендель Е.В., Маслов М.А., Морозова Н.Г., Серебренникова Г.А. Синтез неоглико-липидов для применения в невирусных системах доставки генетического материала // Изв. АН. Сер. хим. 2010. Т. 12. С. 2225–2233.
11. Шмендель Е.В., Тимакова А.А., Маслов М.А., Морозова Н.Г., Чупин В.В. Синтез маннозил-содержащего неогликолипоконъюгата как компонента адресных систем доставки нуклеиновых кислот в антигенпредставляющие клетки // Изв. АН. Сер. хим. 2012. № 7. С. 1480–1484.
Review
For citations:
Shmendel E.V., Eremin S.V., Morozova N.G., Maslov M.A. Synthesis of folate lipoconjugates with hydrophobic spacers. Fine Chemical Technologies. 2013;8(6):111-113. (In Russ.)
Views: 172
Email this article 