Abstract
A novel approach to the synthesis of peptide-oligonucleotide
conjugates (POC) based on the oxathiaphospholane chemistry has been
developed. Peptide and oligonucleotide fragments, which were separately
prepared, were linked postsynthetically by the functionalization
of the peptide either by attachment of the oxathiaphospholane residue
directly at the N-terminus or at the hydroxy group of the linker
connected to N-terminus. The conjugation reaction, based on DBU-assisted
nucleophilic attack of hydroxy group of oligonucleotide on phosphorus
atom in the oxathiaphospholane derivatives of peptide, furnished
the desired POC.
Key words
conjugation - peptides - oligonucleotides - phosphorylations - solid-phase synthesis
References and Notes
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Reaction Conditions: The
synthesis of resin bound tetrathymidine phosphorothioates (4 ) was carried out manually by the syringe
technique on 1 µmol scale and after oligonucleotide-chain
assembly the coupling reaction was performed using 20-fold molar
excess of 3 and 50-fold molar excess of
DBU, coupling time 15 min.
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of 1.2 equiv of DBU in CH2 Cl2 solution. Data for 5 : ³¹ P
NMR (81 MHz, CD3 CN): δ = 60.70, 53.30
ppm. MS-FAB: m/z = 322 [M - 1].
Yield 79%.
18 HPLC analysis were performed using
Econosil C-18 column (4.6 × 250 mm),
1.0 mL/min flow rate; buffer A, 0.1 M TEAB (pH 7.5); buffer
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