123rd General Meeting of the KCS

Type Symposium
Area Current Trends in Organic Chemistry III: Functional Organic Molecules
Room No. Room 301+302
Time FRI 15:20-15:45
Code ORGN3-3
Subject Organic Molecules For Cellular Uptake
Authors Eun-Kyoung Bang
Center for Neuromedicine, Korea Institute of Science and Technology, Korea
Abstract In this talk, we briefly discuss about poly(disulfide)s and amphiphiles for use as novel siRNA transporters. First, dynamic polymers with disulfide repeats in their main chain, were developed to deliver biomolecules through the cellular membrane. We report the synthesis of the counterion propagator units and subsequent polymerization by ring-opening disulfide exchange.[1] We also show that the most active fluorescent poly(disulfide)s reach the cytosol of HeLa cells within 5 min and depolymerize in less than 1 min to release the native substrate. [2] As the second part, we report coordinative amphiphile as a siRNA transporters.[3] As a modification of a conventional cationic lipid structure, we replaced the cationic head with zinc(II)-dipicolylamine complex (Zn/DPA) as a phosphate-directing group, and used various membrane-directing groups in the place of the hydrophobic tails. Interestingly, the Zn/DPA head itself exhibited moderate transfection efficiency, and its combination with various membrane-directing groups enhanced the delivery efficiency without imparting significant cytotoxicity. Thus, it appears possible to develop tunable siRNA transporters simply by changing the membrane-directing parts. These are the first examples of amphiphilic siRNA transporters accompanying coordinative interactions between the amphiphiles and siRNAs. References [1] Bang, E.-K.; Gasparini, G.; Molinard, G.; Roux, A.; Sakai, N.; Matile S. J. Am. Chem. Soc. 2013, 135, 2088–2091. [2] Gasparini, G.; Bang, E.-K.; Molinard, G.; Tulumello, D. V.; Ward, S; Kelley, S. O.; Roux, A.; Sakai, N.; Matile S. J. Am. Chem. Soc. 2014, 136, 6069–6074. [3] Kim, J. B.; Lee, Y. M.; Ryu, J.; Lee, E.; Kim, W. J.; Keum, G.; Bang, E.-K., Bioconjugate Chem. 2016, 27, 1850–1856.
E-mail eunkbang@kist.re.kr