Binding Studies of Cationic Thymidyl Deoxyribonucleic Guanidine to RNA Homopolynucleotides

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-07, Vol.92 (15), p.7051-7055
• Main Authors: Browne, Kenneth A., Dempcy, Robert O., Bruice, Thomas C.
• Format: Article
• Language: English
• Subjects: Antisense Elements (Genetics) - chemistry; Antisense Elements (Genetics) - metabolism; Atoms; Biochemistry; Cations - chemistry; Cations - metabolism; Chemical bases; DNA; DNA - chemistry; DNA - metabolism; Drugs; Guanidines - chemistry; Guanidines - metabolism; Hybridity; Models, Chemical; Models, Molecular; Nucleic Acid Denaturation; Nucleic Acid Heteroduplexes - chemistry; Nucleic acids; Oligonucleotides; Phosphates; Polyribonucleotides - chemistry; Polyribonucleotides - metabolism; Ribonucleic acid; RNA; RNA - chemistry; RNA - metabolism; Sugars
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.15.7051

Deoxyribonucleic guanidine is a potential antisense agent that is generated via the replacement of the negative phosphodiester linkages of DNA [--0--(PO- 2)--0--] with positively-charged guanidinium (g) linkages [--NH--C(=NH+ 2)--NH--]. A pentameric thymidyl deoxyribonucleic guanidine molecule [d(Tg)4T-azido] has been shown to base pair specifically to poly(rA) with an unprecedented affinity. Both double and triple strands consisting of one and two equivalents of d(Tg)4T-azido paired with one equivalent of poly(rA) are indicated by thermal denaturation experiments. At an ionic strength of 0.22, the five bases of d(Tg)4T-azido are estimated to dissociate from a double helix with poly(rA) at >100⚬C! The effect of ionic strength on thermal denaturation is very pronounced, with stability greatest at low ionic strengths. The method of continuous variation indicates that there is an equilibrium complex with a molar ratio of d(Tg) to r(Ap) or d(Ap) of 2:1. Based on this evidence, models of the structures of d(Tg)9T-azido bound to r(Ap)9A are proposed.