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A New and Efficient Method for Synthesis of 5′‐Conjugates of Oligonucleotides through Amide‐Bond Formation on Solid Phase
Author(s) -
Kachalova Anna V.,
Stetsenko Dmitry A.,
Romanova Elena A.,
Tashlitsky Vadim N.,
Gait Michael J.,
Oretskaya Tatiana S.
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200208)85:8<2409::aid-hlca2409>3.0.co;2-p
Subject(s) - phosphoramidite , chemistry , oligonucleotide , moiety , amide , solid phase synthesis , oligonucleotide synthesis , combinatorial chemistry , conjugate , conjugated system , protecting group , peptide bond , peptide , yield (engineering) , carboxylic acid , peptide synthesis , organic chemistry , stereochemistry , polymer , biochemistry , dna , mathematical analysis , alkyl , materials science , mathematics , metallurgy
An efficient method for synthesis of oligonucleotide 5′‐conjugates through amide‐bond formation on solid phase is described. Protected oligonucleotides containing a 5′‐carboxylic acid function were obtained by use of a novel non‐nucleosidic phosphoramidite building block, where the carboxylic acid moiety was protected by a 2‐chlorotrityl group. The protecting group is stable to the phosphoramidite coupling conditions used in solid‐phase oligonucleotide assembly, but is easily deprotected by mild acidic treatment. The protecting group may be removed also by ammonolysis. 5′‐Carboxylate‐modified oligonucleotides were efficiently conjugated on solid support under normal peptide‐coupling conditions to various amines or to the N‐termini of small peptides to yield products of high purity. The method is well‐suited in principle for the synthesis of peptide‐oligonucleotide conjugates containing an amide linkage between the 5′‐end of an oligonucleotide and the N‐terminus of a peptide.