Gas-phase Dissociation of homo-DNA Oligonucleotides

Synthetic modified oligonucleotides are of interest for diagnostic and therapeutic applications, as their biological stability, pairing selectivity, and binding strength can be considerably increased by the incorporation of unnatural structural elements. Homo-DNA is an oligonucleotide homologue based on dideoxy-hexopyranosyl sugar moieties, which follows the Watson-Crick A-T and G-C base pairing system, but does not hybridize with complementary natural DNA and RNA. Homo-DNA has found application as a bioorthogonal element in templated chemistry applications. The gas-phase dissociation of homo-DNA has been investigated by ESI-MS/MS and MALDI-MS/MS, and mechanistic aspects of its gas-phase dissociation are discussed. Experiments revealed a charge state dependent preference for the loss of nucleobases, which are released either as neutrals or as anions. In contrast to DNA, nucleobase loss from homo-DNA was found to be decoupled from backbone cleavage, thus resulting in stable products. This renders an additional stage of ion activation necessary in order to generate sequence-defining fragment ions. Upon MS(3) of the primary base-loss ion, homo-DNA was found to exhibit unspecific backbone dissociation resulting in a balanced distribution of all fragment ion series.

Nucleic acid sensing by an orthogonal reporter system based on homo-DNA

We have developed an assay for single strand DNA or RNA detection which is based on the homo-DNA templated Staudinger reduction of the profluorophore rhodamine-azide. The assay is based on a three component system, consisting of a homo-DNA/DNA hybrid probe, a set of homo-DNA reporter strands and the target DNA or RNA. We present two different formats of the assay (Omega probe and linear probe) in which the linear probe was found to perform best with catalytic turnover of the reporter strands (TON: 8) and a match/mismatch discrimination of up to 19. The advantage of this system is that the reporting (homo-DNA) and sensing (DNA) domain are decoupled from each other since the two pairing systems are bioorthogonal. This allows independent optimization of either domain which may lead to higher selectivity in in vivo imaging.

Molecular beacons with a homo-DNA stem: improving target selectivity

Molecular beacons (MBs) are stem-loop DNA probes used for identifying and reporting the presence and localization of nucleic acid targets in vitro and in vivo via target-dependent dequenching of fluorescence. A drawback of conventional MB design is present in the stem sequence that is necessary to keep the MBs in a closed conformation in the absence of a target, but that can participate in target binding in the open (target-on) conformation, giving rise to the possibility of false-positive results. In order to circumvent these problems, we designed MBs in which the stem was replaced by an orthogonal DNA analog that does not cross-pair with natural nucleic acids. Homo-DNA seemed to be specially suited, as it forms stable adenine-adenine base pairs of the reversed Hoogsteen type, potentially reducing the number of necessary building blocks for stem design to one. We found that MBs in which the stem part was replaced by homo-adenylate residues can easily be synthesized using conventional automated DNA synthesis. As conventional MBs, such hybrid MBs show cooperative hairpin to coil transitions in the absence of a DNA target, indicating stable homo-DNA base pair formation in the closed conformation. Furthermore, our results show that the homo-adenylate stem is excluded from DNA target binding, which leads to a significant increase in target binding selectivity

Zusammenhänge zwischen sozialer Unterstützung und Suizidalität bei homo- und bisexuellen Personen

Der Beitrag untersucht Zusammenhänge zwischen sozialer Unterstützung und Suizidalität bei 615 homo- und bisexuellen Personen in der Schweiz. In einer Internetumfrage wurden dazu Suizidgedanken, Suizidpläne und Suizidversuche, sowie diverse Aspekte sozialer Unterstützung und die soziale Belastung erfragt. Obwohl homo- und bisexuelle Personen hohe Werte sozialer Unterstützung und niedrige Werte sozialer Belastung aufwiesen, zeigten sich hohe 12-Monats- und Lebenszeitprävalenzen bezüglich Suizidgedanken, -plänen und -versuchen. Alle Aspekte sozialer Unterstützung waren mit der Suizidalität in den letzten zwölf Monaten assoziiert, wobei die Zusammenhänge mit der sozialen Integration (r = -.34) und der sozialen Belastung (r = .39) am stärksten ausfielen. Selbst bei Kontrolle der depressiven Stimmung und des Alters teilnehmender Personen blieben die soziale Unterstützung (OR = .61) und die soziale Belastung (OR = 2.13) prädiktiv für die Suizidalität in den letzten zwölf Monaten. Personen, die viel soziale Unterstützung wahrnahmen (> 1 SD über dem Mittelwert) berichteten fünfmal weniger Suizidalität als solche mit geringer sozialer Unterstützung (> 1 SD unter dem Mittelwert). Personen, die viel soziale Belastung in ihrem Umfeld wahrnahmen (> 1 SD über dem Mittelwert), zeigten im vergangenen Jahr 14-mal häufiger Suizidalität als Personen, die geringe soziale Belastung erlebten (> 1 SD unter dem Mittelwert).

HOMO Stabilisation in π-Extended Dibenzotetrathiafulvalene Derivatives for Their Application in Organic Field-Effect Transistors

Three new organic semiconductors, in which either two methoxy units are directly linked to a dibenzotetrathiafulvalene (DB-TTF) central core and a 2,1,3-chalcogendiazole is fused on the one side, or four methoxy groups are linked to the DB-TTF, have been synthesised as active materials for organic field-effect transistors (OFETs). Their electrochemical behaviour, electronic absorption and fluorescence emission as well as photoinduced intramolecular charge transfer were studied. The electron-withdrawing 2,1,3-chalcogendiazole unit significantly affects the electronic properties of these semiconductors, lowering both the HOMO and LUMO energy levels and hence increasing the stability of the semiconducting material. The solution-processed single-crystal transistors exhibit high performance with a hole mobility up to 0.04 cm2 V−1 s−1 as well as good ambient stability.