Purine DNA Constructs Designed to Expand the Genetic Code: Functionalization, Impact of Ionic Forms, and Molecular Recognition of 7-Deazaxanthine-7-Deazapurine-2,6-diamine Base Pairs and Their Purine Counterparts
Autor(en): | Chandankar, Somnath Shivaji Kondhare, Dasharath Leonard, Peter Seela, Frank |
Stichwörter: | 2'-DEOXYXANTHOSINE; Chemistry; Chemistry, Organic; ISOGUANINE; NUCLEIC-ACIDS; NUCLEOTIDES; OLIGONUCLEOTIDE DUPLEXES; PARALLEL; PROTECTION; STABILITY; SUBSTRATE PROPERTIES; XANTHOSINE | Erscheinungsdatum: | 2023 | Herausgeber: | AMER CHEMICAL SOC | Journal: | JOURNAL OF ORGANIC CHEMISTRY | Volumen: | 88 | Ausgabe: | 18 | Startseite: | 13149 | Seitenende: | 13168 | Zusammenfassung: | Purine DNA represents an alternative pairing system formed by two purines in the base pair with the recognition elements of Watson-Crick DNA. Base functionalization of 7-deaza2 `-deoxyxanthosine with ethynyl and octadiynyl residues led to clickable side chain derivatives with short and long linker arms. As complementary bases, purine-2,6-diamine or 7-deazapurine-2,6diamine 2 `-deoxyribonucleosides were used. 7-Deaza-7-iodo-2 ` deoxyxanthosine served as a starting material for Sonogashira cross-coupling and the p-nitrophenylethyl group for base protection. Phosphoramidite building blocks for DNA synthesis were prepared. Oligonucleotides containing single modifications or runs of three purine base pairs embedded in 12-mer Watson-Crick DNA were synthesized and hybridized with complementary strands with purine- or 7-deazapurine-2,6-diamine located opposite to the xanthine derivatives. The stability of base pairs was evaluated in a comparative study on the basis of DNA melting experiments and Tm values. As 7-deazaxanthine and xanthine nucleosides form anionic forms at neutral pH, duplex stability became pK-dependent, and the system with 7-deazapurine displayed a significant higher stability as that containing xanthine. Alkynyl side chains are well accommodated in the purine-purine helix. Click adducts with pyrene showed that short linker arms destabilize duplexes, whereas long linkers increase duplex stability. CD and fluorescence measurements provide further insights into purine-purine base pairing. |
ISSN: | 0022-3263 | DOI: | 10.1021/acs.joc.3c01370 |
Zur Langanzeige