A1 Refereed original research article in a scientific journal
Solid-Supported Synthesis and Click Conjugation of 4 '-C-Alkyne Functionalized Oligodeoxyribonucleotides
Authors: Kiviniemi A, Virta P, Lonnberg H
Publisher: AMER CHEMICAL SOC
Publication year: 2010
Journal: Bioconjugate Chemistry
Journal name in source: BIOCONJUGATE CHEMISTRY
Journal acronym: BIOCONJUGATE CHEM
Number in series: 10
Volume: 21
Issue: 10
First page : 1890
Last page: 1901
Number of pages: 12
ISSN: 1043-1802
DOI: https://doi.org/10.1021/bc100268w
Abstract
4'-C-[N,N-Di(4-pentyn-l-yl)aminomethyl]thymidine and 4'-C-[N-methyl-N-(4-pentyn-l-yl)aminomethyl]thymidine 3'-(2-cyanoethyl-N,N-diisopropyl)phosphoramidites (1, 2) were synthesized, and one or two such monomers were incorporated into a 15-mer oligodeoxyribonucleotide. After chain assembly, azido-functionalized ligands, including appropriate derivatives of 1,4-phenylenedimethaneamine, mannose, paromamine, and neomycin, were conjugated to the alkynyl groups by the click chemistry on a solid support. The influence of the 4'-modifications on the melting temperature with DNA and 2'-O-methyl RNA targets was studied. Oligonucleotides containing one to four mannose ligands in the central part of the chain (up to two 4'-C-[N,N-di(4-pentyn-l-yl)aminomethyl]thymidine units) form equally stable duplexes with complementary 2'-OMe RNA as the corresponding unmodified DNA sequence. At high salt content, the mannose conjugation is even stabilizing. On using a DNA target, a modest destabilization occurs. All the amino group bearing conjugates stabilized the duplexes, the DNA.DNA duplexes more than the DNA.2'-O-methyl RNA duplexes.
4'-C-[N,N-Di(4-pentyn-l-yl)aminomethyl]thymidine and 4'-C-[N-methyl-N-(4-pentyn-l-yl)aminomethyl]thymidine 3'-(2-cyanoethyl-N,N-diisopropyl)phosphoramidites (1, 2) were synthesized, and one or two such monomers were incorporated into a 15-mer oligodeoxyribonucleotide. After chain assembly, azido-functionalized ligands, including appropriate derivatives of 1,4-phenylenedimethaneamine, mannose, paromamine, and neomycin, were conjugated to the alkynyl groups by the click chemistry on a solid support. The influence of the 4'-modifications on the melting temperature with DNA and 2'-O-methyl RNA targets was studied. Oligonucleotides containing one to four mannose ligands in the central part of the chain (up to two 4'-C-[N,N-di(4-pentyn-l-yl)aminomethyl]thymidine units) form equally stable duplexes with complementary 2'-OMe RNA as the corresponding unmodified DNA sequence. At high salt content, the mannose conjugation is even stabilizing. On using a DNA target, a modest destabilization occurs. All the amino group bearing conjugates stabilized the duplexes, the DNA.DNA duplexes more than the DNA.2'-O-methyl RNA duplexes.
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