TY - JOUR

T1 - New Zwitter-Ionic Oligonucleotides: Preparation and Complementary Binding

AU - Patrushev, D. E.

AU - Burakova, E. A.

AU - Bizyaev, S. N.

AU - Fokina, A. A.

AU - Stetsenko, D. A.

N1 - The work was supported by the Russian Science Foundation (grant no. 22-13-00212), and the Ministry of Science and Higher Education of the Russian Federation (Novosibirsk State University project FSUS-2020-0035). Публикация для корректировки.

PY - 2023/4

Y1 - 2023/4

N2 - New zwitter-ionic oligonucleotide derivatives containing 1,2,3,4-tetrahydroisoquinoline-7-sulfonyl phosphoramidate group are described. Automated synthesis of these compounds was carried out according to the β-cyanoethyl phosphoramidite scheme via the Staudinger reaction between 2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl azide and phosphite triester within oligonucleotide grafted to polymer support. 1,2,3,4-Tetrahydroisoquinoline-7-sulfonyl phosphoramidate group (THIQ) was stable under the conditions of standard oligonucleotide synthesis, including the removal of protective groups and cleavage of the oligonucleotide from the polymer support by treatment with a mixture of concentrated aqueous solutions of ammonia and methylamine (1 : 1) at 55°C. Oligonucleotides modified by one to five THIQ groups in various positions were obtained. The zwitter-ionic character of the obtained derivatives was reflected in their varying mobility under conditions of denaturing PAGE. The thermal stability of the duplexes of oligodeoxynucleotides containing THIQ groups with complementary DNA and RNA only slightly differed from that of natural DNA:DNA and DNA:RNA duplexes. The results reported suggest that oligonucleotides modified with zwitter-ionic THIQ groups as antisense therapeutic agents.

AB - New zwitter-ionic oligonucleotide derivatives containing 1,2,3,4-tetrahydroisoquinoline-7-sulfonyl phosphoramidate group are described. Automated synthesis of these compounds was carried out according to the β-cyanoethyl phosphoramidite scheme via the Staudinger reaction between 2-trifluoroacetyl-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl azide and phosphite triester within oligonucleotide grafted to polymer support. 1,2,3,4-Tetrahydroisoquinoline-7-sulfonyl phosphoramidate group (THIQ) was stable under the conditions of standard oligonucleotide synthesis, including the removal of protective groups and cleavage of the oligonucleotide from the polymer support by treatment with a mixture of concentrated aqueous solutions of ammonia and methylamine (1 : 1) at 55°C. Oligonucleotides modified by one to five THIQ groups in various positions were obtained. The zwitter-ionic character of the obtained derivatives was reflected in their varying mobility under conditions of denaturing PAGE. The thermal stability of the duplexes of oligodeoxynucleotides containing THIQ groups with complementary DNA and RNA only slightly differed from that of natural DNA:DNA and DNA:RNA duplexes. The results reported suggest that oligonucleotides modified with zwitter-ionic THIQ groups as antisense therapeutic agents.

KW - Staudinger reaction

KW - antisense oligonucleotides

KW - solid-phase synthesis

KW - sulfonyl azide

KW - zwitter ion

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85156123510&origin=inward&txGid=e7a89eb24bf7250c89b982dfbf8f9be9

UR - https://www.mendeley.com/catalogue/0f5e365d-161f-3648-9cf6-3688bcc8d72d/

U2 - 10.1134/S0026893323020164

DO - 10.1134/S0026893323020164

M3 - Article

VL - 57

SP - 320

EP - 328

JO - Molecular Biology

JF - Molecular Biology

SN - 0026-8933

IS - 2

ER -