Trisoligonucleotides with a C3h-symmetric linker
The trisoligonucleotides consist of three linear oligonucleotides which are connected at their 3'-ends by a C3h-symmetric organic linker, which was chosen to assure that all strands experience the same conformational constraints (Scheme 1).
Scheme 1 A) Trisoligonucleotide synthesis: 1) The first strand is assembled in 5'-3' direction using "reverse" 5'-nucleoside amidites. 2) Trislinker amidite 4 is coupled and subsequently detritylated. 3) The second strand is synthesized in 3'-5' direction using common 3'-nucleoside amidites. 4) After Pd-catalyzed removal of the AOC protecting group, the third strand is again assembled in 3'-5' direction. B) Synthesis of the trislinker amidite: a) 0.85 eq. allyloxycarbonyl chloride (AOC-Cl), 0.85 eq. pyridine, THF; b) 0.85 eq. 4,4´-dimethoxytrityl chloride (DMT-Cl), pyridine; c) 1.3 eq 2-cyanoethyl N,N,N',N'-tetraisopropylaminophosphorodiamidite, 1.3 eq diisopropylammonium tetrazolide, dichloromethane. Yields calculated after chromatographic purification.