Acyclic Nucleoside Phosphonates Bearing (R)‐ or (S)‐9‐[3‐Hydroxy‐2‐(phosphonoethoxy)propyl] (HPEP) Moiety as Monomers for the Synthesis of Modified Oligonucleotides

• Published in: European journal of organic chemistry Vol. 2018; no. 37; pp. 5119 - 5126
• Main Authors: Kaiser, Martin Maxmilian, Novák, Pavel, Rosenbergová, Šárka, Poštová‐Slavětínská, Lenka, Rosenberg, Ivan, Janeba, Zlatko
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 09.10.2018; Wiley Subscription Services, Inc
• Subjects: Chemistry; Chemistry, Organic; Deoxyribonucleic acid; DNA; Duplexes; Hybridization; Monomers; Nonamers; Nucleobases; Oligonucleotides; Phosphonates; Physical Sciences; Ribonucleic acid; RNA; Science & Technology; Solid phase synthesis; Solid phases; Thermal stability; Thymine; Tm values; Nonamers; T-m values; DNA VIRUS; ANALOGS; Oligonucleotides; Duplexes; CRYSTAL-STRUCTURES; Hybridization; 6-OXOPURINE PHOSPHORIBOSYLTRANSFERASES; Nucleobases; HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE; PLASMODIUM-FALCIPARUM; PRODRUGS; SELECTIVE INHIBITORS; OLIGORIBONUCLEOTIDES; DUPLEX
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201800490

Suitably protected (R)‐ and (S)‐HPEP {9‐[3‐hydroxy‐2‐(phosphonoethoxy)propyl]} derivatives containing adenine and thymine nucleobases were prepared as monomers for the introduction of acyclic nucleotide units into oligonucleotides. The solid phase synthesis of a series of ribo and 2′‐deoxyribo nonamers containing (R)‐HPEP and (S)‐HPEP units was successfully performed in both 5′ → 3′ and 3′ → 5′ directions. The measurement of thermal characteristics of the complexes of modified nonamers with complementary DNA and RNA strands revealed a general destabilizing effect of the introduced acyclic units on the thermal stability, but in several cases [modif.RNA*RNA and modif.DNA*RNA with (S)‐HPEPA units], the duplexes were characterized in terms of Tm values. A solid‐phase synthesis afforded a series of ribo and 2′‐deoxyribo nonamers containing acyclic nucleotide units. A general destabilizing effect of the introduced acyclic units on the thermal stability of complexes of modified nonamers with the complementary DNA and RNA strands was observed, but in cases with (S)‐HPEPA units, the duplexes were characterized in terms of Tm values.