Biophysical and RNA interference inhibitory properties of oligonucleotides carrying tetrathiafulvalene groups at terminal positions

Oligonucleotide conjugates carrying a single functionalized tetrathiafulvalene (TTF) unit linked through a threoninol molecule to the 3′ or 5′ ends were synthesized together with their complementary oligonucleotides carrying a TTF, pyrene, or pentafluorophenyl group. TTF-oligonucleotide conjugates formed duplexes with higher thermal stability than the corresponding unmodified oligonucleotides and pyrene- and pentafluorophenyl-modified oligonucleotides. TTF-modified oligonucleotides are able to bind to citrate-stabilized gold nanoparticles (AuNPs) and produce stable gold AuNPs functionalized with oligonucleotides. Finally, TTF- oligoribonucleotides have been synthesized to produce siRNA duplexes carrying TTF units. The presence of the TTF molecule is compatible with the RNA interference mechanism for gene inhibition.The authors thank Dr. Anna Avi˜n´o for providing the nonmodified oligonucleotides 11–14.This researchwas supported by the European Commission (Grants FP7-FUNMOL 213382 and NMP4-LA-2011-262943, MULTIFUN), by the Spanish Ministry of Education (grant CTQ2010-20541, SAF2010-15440), the Generalitat de Catalunya (2009/SGR/208), the Czech Science Foundation (P207/10/2214), the Ministry of Education, Youth and Sports of the Czech Republic (7E09054), and the Institute of Organic Chemistry and Biochemistry AS CR (RVO: 61388963). The authors declare no conflict of interests.Peer reviewe