Search

Dodecamer duplex DNA containing anomeric (α/β‐d) and enantiomeric (β‐l/β‐d) 2'‐deoxycytidine mismatches was studied with respect to base pair stability in the absence and presence of silver ions. Stable duplexes with silver‐mediated cytosine–cytosine pairs were formed by all anomeric and enantiomeric combinations. Stability changes were observed depending on the composition of the mismatches. Most strikingly, the new silver‐mediated base pair of anomeric α‐d‐dC with enantiomeric β‐l‐dC is superior to the well‐noted β‐d/β‐d‐dC pair in terms of stability. CD spectra were used to follow global helical changes of DNA structure. [ABSTRACT FROM AUTHOR]

Silver‐mediated α‐dC–Ag+–β‐dC hybrid base pairs decorated with 5‐iodo‐ or 5‐octadiynyl residues are well accommodated in duplex DNA. A strong Tm increase and favorable thermodynamic data for duplex DNA were observed after addition of silver ions. The phenomenon is particularly obvious when both nucleobases of the base pairs are functionalized. Neither the position of the base pair, nor the type of 5‐substituent had a negative influence. On the contrary, functionalization of conventional silver‐mediated β‐dC–Ag+–β‐dC homo base pairs showed a negative impact induced by the bulky substituents. To this end, cytosine modified 12‐mer oligodeoxynucleotides were prepared by solid‐phase synthesis employing new α‐anomeric 2′‐deoxycytidine phosphoramidites. A multigram scale synthesis was developed for 5‐iodo‐α‐d‐2′‐deoxycytidine (1) employing the direct glycosylation of cytosine with Hoffer's α‐d‐halogenose followed by separation of anomeric DMT nucleosides. Regarding base‐pair stability and functionalization silver‐mediated α/β‐dC hybrid base pairs were found to be superior to β/β‐dC homo pairs. According to their extraordinary properties, they might find applications in DNA diagnostics, material science, or nanotechnology. DNA structures: Silver‐mediated α‐dC–Ag+–β‐dC hybrid base pairs decorated with bulky residues are well accommodated in duplex DNA. Silver‐mediated α/β‐dC hybrid base pairs are superior to β/β‐dC homo pairs with regard to base‐pair stability, impact of 5‐substituents, and mismatch discrimination. These properties might find application in DNA diagnostics, material science, or nanotechnology (see figure). [ABSTRACT FROM AUTHOR]

Halogenated nucleosides, such as 5‐iodo‐2′‐deoxyuridine and 5‐iodo‐2′‐deoxycytidine, are incorporated into the DNA of replicating cells to facilitate DNA single‐strand breaks and intra‐ or interstrand crosslinks upon UV irradiation. In this work, it is shown that the naphthyl‐based organoselenium compounds can mediate the dehalogenation of halogenated pyrimidine‐based nucleosides, such as 5‐X‐2′‐deoxyuridine and 5‐X‐2′‐deoxycytidine (X=Br or I). The rate of deiodination was found to be significantly higher than that of the debromination for both nucleosides. Furthermore, the deiodination of iodo‐cytidines was found to be faster than that of iodo‐uridines. The initial rates of the deiodinations of 5‐iodocytosine and 5‐iodouracil indicated that the nature of the sugar moiety influences the kinetics of the deiodination. For both the nucleobases and nucleosides, the deiodination and debromination reactions follow a halogen‐bond‐mediated and addition/elimination pathway, respectively. DNA photosensitizers: Dehalogenation of halogenated nucleosides, which are potential DNA photosensitizers, by organoselenium compounds is described (see picture). Attachment of 2′‐deoxyribose or ribose sugar to the halogenated nucleobases significantly enhances the rate of deiodination reactions. The Se⋅⋅⋅I halogen bonding plays an important role in the kinetics of the deiodination reactions. [ABSTRACT FROM AUTHOR]

Abstract: 5‐Aza‐7‐deaza‐2′‐deoxyguanosine (dZ) forms a silver‐mediated base pair with dC. The metal ion pair represents a mimic of the H‐bonded Watson–Crick dG‐dC pair. The modified nucleoside displays a similar shape as the parent 2′‐deoxyguanosine from which it can be constructed by transposition of nitrogen‐7 to the bridgehead position‐5. It lacks the major groove binding site as the positional change moves the dG‐ acceptor position from nitrogen‐7 to nitrogen‐1. As a shape mimic of dG, it fits nicely in the DNA double helix. The purine–pyrimidine dZ‐dC hetero pair shows a relationship to the pyrimidine–pyrimidine dC‐dC homo base pair. The dZ‐dC pair forms a mismatch in the absence of silver ions and matches after addition of metal ions. Base‐pair formation was verified on self‐complementary 6‐mer duplexes and 12‐mer DNA with random composition by UV‐dependent Tm measurements. Modified silver‐mediated and hydrogen‐bonded canonical base pairs can coexist. The dZ‐Ag+‐dC base pair is slightly less stable than the dG‐dC pair, shows sequence dependence, and consumes one or two silver ions. These properties make the dZ‐Ag+‐dC pair suitable for programmable incorporation of silver ions in DNA which cannot be achieved by canonical base pairs. If the silver ion content is higher than the total number of base pairs the duplexes turn into very stable structures in which all base pairs are considered to be in the silver‐mediated pairing mode. [ABSTRACT FROM AUTHOR]

5-Hydroxymethyl-, 5-formyl-, and 5-carboxy-2′-deoxycytidine are new epigenetic bases (hmdC, fdC, cadC) that were recently discovered in the DNA of higher eukaryotes. The same bases (5-hydroxymethyl-, 5-formyl-, and 5-carboxycytidine; hmC, fC, and caC) have now also been detected in mammalian RNA with a high abundance in mRNA. While DNA phosphoramidites (PAs) that allow the synthesis of xdC-containing oligonucleotides for deeper biological studies are available, the corresponding silyl-protected RNA PAs for fC and caC have not yet been disclosed. Here, we report novel RNA PAs for hmC, fC, and caC that can be used in routine RNA synthesis. The new building blocks are compatible with the canonical PAs and also with themselves, which enables even the synthesis of RNA strands containing all three of these bases. The study will pave the way for detailed physical, biochemical, and biological studies to unravel the function of these non-canonical modifications in RNA. [ABSTRACT FROM AUTHOR]