Synthesis of oligonucleotide 2'-conjugates via amide bond formation in solution.
An efficient method for synthesis of 2'-O-carboxymethyl oligonucleotides is described. Fully deprotected oligonucleotides containing a carboxymethyl group at the 2'-position of sugar residue were obtained by a two-step procedure by periodate cleavage of an oligonucleotide containing 1,2-diol group followed by oxidation of the 2'-aldehyde resulted with sodium chlorite. 2'-O-Carboxymethyl oligonucleotides prepared were efficiently coupled in aqueous solution in the presence of a water-soluble carbodiimide to a number of amino acid derivatives or short peptides to afford novel 2'-conjugates of high purity in good yield. The method is thus shown to be suitable in principle for preparation of oligonucleotide-peptide conjugates containing an amide linkage between the 2'-carboxy group of a modified oligonucleotide and the amino terminus of a peptide.
Kachalova
Anna V
AV
Chemistry Department, M. V. Lomonossov Moscow State University, Leninskie Gory, Moscow 119992, Russia.
Stetsenko
Dmitry A
DA
Gait
Michael J
MJ
Oretskaya
Tatiana S
TS
D000577:Amides / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification; D009842:Oligopeptides / Q000138:chemical synthesis / Q000302:isolation & purification; D012996:Solutions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000577:Amides; D009841:Oligonucleotides; D009842:Oligopeptides; D012996:Solutions