Extraordinary thermal stability of an oligodeoxynucleotide octamer constructed from alternating 7-deaza-7-iodo guanine and 5-Iodocytosine base pairs - DNA duplex stabilization by halogen bonds?

A reinvestigation of the published X-ray crystal-structure analyses of 7-halogenated (Br, I) 8-aza-7-deaza-2'-deoxyguanosines Br(7) c(7) z(8) Gd ; 1a and I(7) c(7) z(8) Gd , 1b, as well as of the structurally related 7-deaza-7-iodo-2'-deoxy-β-D-ribofuranosyladenine (β-I(7) c(7) Ad ; 2=6e in Table 1) and its α-D-anomer (α-I(7) c(7) Ad ; 3) clearly revealed the existence of halogen bonds between corresponding halogen substituents and the adjacent N(3)-atoms of neighboring nucleoside molecules within the single crystals. These halogen bonds can be rationalized by the presence of a region of positive electrostatic potential, the σ-hole, on the outermost portion the halogen's surface, while the three unshared pairs of electrons produce a belt of negative electrostatic potential around the central part of the halogen substituent. The N(3) atoms of the halogenated nucleosides carry a partial negative charge.

Hoogsteen vs. Watson-Crick base pairing: incorporation of 2-substituted adenine- and 7-deazaadenine 2'-deoxy-beta-D-ribonucleosides into oligonucleotides.

Various 2-substituted 2'-deoxyadenosines and 7-deazaadenosines have been synthesized. The phosphonate building block 9 of 2-chloro-7-deaza-2'-deoxyadenosine (7-deazacladribine; 2) was prepared by 4,4'-dimethoxytritylation of the parent nucleoside (-->7), followed by protection of the amino function with a formamidine residue (-->8). The latter was reacted with PCl3/N-methylmorpholine/1,2,4-triazole to give compound 9.

Oligonucleotides incorporating 7-(aminoalkyn-1-yl)-7-deaza-2'-deoxyguanosines: duplex stability and phosphodiester hydrolysis by exonucleases.

Self-complementary [[5'-d(G-C)4]2] and non-selfcomplementary oligonucleotides [5'-d(TAG GTC AAT ACT) x 3'-d(ATC CAG TTA TGA)] containing 7-(omega-aminoalkyn-1-yl)-7-deaza-2'-deoxyguanosines (1a-c) (1) and 7-deaza-2'-deoxyguanosine instead of dG were studied regarding their thermal stability as well as their phosphodiester hydrolysis by either 3' --> 5'- or 5' --> 3'-phosphodiesterase studied by MALDI-TOF MS.

Oligonucleotides incorporating 7-(aminoalkynyl)-7-deaza-2'-deoxyguanosines: duplex stability and phosphodiester hydrolysis by exonucleases.

Oligonucleotides containing 7-(omega-aminoalkyn-1-yl)-7-deaza-2'-deoxyguanosines (1a-c) were investigated regarding their thermal stability (T(m) values) as well as their phosphodiester hydrolysis catalyzed by exonucleases. Those derivatives are suitable for the labeling of nucleic acid constituents as well as for the postlabeling of DNA. For this, the phosphoramidites 7a,c (obtained from the nucleoside 1a,b), protected by an isobutyryl group at the 2-amino group and a phthaloyl residue at the side-chain amino function, were synthesized.

2-aza-2'-deoxyadenosine: synthesis, base-pairing selectivity, and stacking properties of oligonucleotides.

2-Aza-2'-deoxyadenosine (2, z2Ad) is synthesized via its 1,N6-etheno derivative 7 and enzymatically deaminated to 2-aza-2'-deoxyinosine (3). Compound 2 is converted into the phosphoramidite building block 10b. This is employed in solid-phase oligonucleotide synthesis.

Phosphoramidites and oligonucleotides containing 7-deazapurines and pyrimidines carrying aminopropargyl side chains.

The synthesis of phosphoramidites containing 7-deazaguanine, 7-deazaadenine, uracil and cytosine carrying aminopropargyl chains is described. The corresponding oligonucleotides are stabilized in duplexes thermally as well as against degradation by exonucleases.

Fluorescent DNA: the development of 7-deazapurine nucleoside triphosphates applicable for sequencing at the single molecule level.

7-Deaza-2'-deoxyadenosine and -guanosine phosphoramidite building blocks as well as corresponding 5'-triphosphate derivatives are described carrying in position 7 substituents such as iodo, hexyn-1-yl or 5-aminopentyn-1-yl residues. The phosphoramidites were used to synthesize a series of modified oligodeoxynucleotides. A systematic study of the thermal stabilities of these oligonucleotide duplexes demonstrated that the 7-substituents are well accommodated in the major groove of B-DNA.

Photochemical conversion of oligonucleotides containing 2-chloro-2'-deoxyadenosine: enhanced UV sensitivity of a modified purine base induced by the nearest neighbor.

Irradiation of alternating dodecamers containing 2-chloro-2'-deoxyadenosine (Cl2dAdo) with ultraviolet light (254 nm) has been investigated. The photoconversion of Cl2dAdo into 2'-deoxyisoguanosine (isodGuo) and the completeness of the reaction were studied by reversed-phase HPLC and UV absorption spectra. The photosensitivity of Cl2dAdo within an oligonucleotide was found to be sequence-specific and depends on the nearest neighbor; 2'-deoxyguanosine residues accelerate the rate of photoconversion by a factor of 3.

Purine nucleoside phosphorylase: inhibition by purine N(7)- and N(9)-acyclonucleosides; and substrate properties of 7-beta-D-ribofuranosylguanine and 7-beta-D-ribofuranosylhypoxanthine.

A series of 10 N(7)- and N(9)-acyclonucleosides of guanine and 8-substituted guanines (8-Br, 8-SH and 8-NH2), and two N(7)-acyclonucleosides of hypoxanthine, were tested for their ability to inhibit purine nucleoside phosphorylase (PNP) (E.C. 2.