Synthetic studies towards a novel, chemical stable, abasic site analogue of DNA

We synthesized the phosphinate 7 via photoaddition of methanol to the alpha, beta unsaturated deoxyribono lactone as the key step, followed by an Arbusov reaction for the introduction of phosphorous. Precursor 7 serves for the synthesis and incorporation into DNA of a novel chemically stable abasic site analogue that might act as an inhibitor for DNA glycosylases

Transition metal ligands as novel DNA-base substitutes

The base modified nucleoside dBP, carrying a non-hydrogen-bonding non-shape complementary base was incorporated into oligonucleotides (Brotschi, C.; Haberli, A.; Leumann C.J. Angew. Chem. Int. Ed. 2001, 40, 3012-3014). This base was designed to coordinate transition metal ions into well defined positions within a DNA double helix. Melting experiments revealed that the stability of a dBP:dBP base couple in a DNA duplex is similar to a dG:dC base pair even in the absence of transition metal ions. In the presence of transition metal ions, melting experiments revealed a decrease in duplex stability which is on a similar order for all metal ions (Mn2+, Cu2+, Zn2+, Ni2+) tested

DNA with Hydrophobic Base Substitutes: A Stable, Zipperlike Recognition Motif Based On Interstrand-Stacking Interactions

No Abstract

Thermal acclimation to 4 or 10 degrees C imparts minimal benefit on swimming performance in Atlantic cod (Gadus morhua L.).

Thermal acclimation is frequently cited as a means by which ectothermic animals improve their Darwinian fitness, i.e. the beneficial acclimation hypothesis. As the critical swimming speed (U (crit)) test is often used as a proxy measure of fitness, we acclimated Atlantic cod (Gadus morhua) to 4 and 10 degrees C and then assessed their U (crit) swimming performance at their respective acclimation temperatures and during acute temperature reversal. Because phenotypic differences exist between different populations of cod, we undertook these experiments in two different populations, North Sea cod and North East Arctic cod. Acclimation to 4 or 10 degrees C had a minimal effect on swimming performance or U (crit), however test temperature did, with all groups having a 10-17% higher U (crit) at 10 degrees C. The swimming efficiency was significantly lower in all groups at 4 degrees C arguably due to the compression of the muscle fibre recruitment order. This also led to a reduction in the duration of "kick and glide" swimming at 4 degrees C. No significant differences were seen between the two populations in any of the measured parameters, due possibly to the extended acclimation period. Our data indicate that acclimation imparts little benefit on U (crit) swimming test in Atlantic cod. Further efforts need to identify the functional consequences of the long-term thermal acclimation process.

One-Step (18)F-Labeling of Carbohydrate-Conjugated Octreotate-Derivatives Containing a Silicon-Fluoride-Acceptor (SiFA): In Vitro and in Vivo Evaluation as Tumor Imaging Agents for Positron Emission Tomography (PET)

The synthesis, radiolabeling, and initial evaluation of new silicon-fluoride acceptor (SiFA) derivatized octreotate derivatives is reported. So far, the main drawback of the SiFA technology for the synthesis of PET-radiotracers is the high lipophilicity of the resulting radiopharmaceutical. Consequently, we synthesized new SiFA-octreotate analogues derivatized with Fmoc-NH-PEG-COOH, Fmoc-Asn(Ac?AcNH-?-Glc)-OH, and SiFA-aldehyde (SIFA-A). The substances could be labeled in high yields (38 ± 4%) and specific activities between 29 and 56 GBq/?mol in short synthesis times of less than 30 min (e.o.b.). The in vitro evaluation of the synthesized conjugates displayed a sst2 receptor affinity (IC?? = 3.3 ± 0.3 nM) comparable to that of somatostatin-28. As a measure of lipophilicity of the conjugates, the log P(ow) was determined and found to be 0.96 for SiFA-Asn(AcNH-?-Glc)-PEG-Tyr³-octreotate and 1.23 for SiFA-Asn(AcNH-?-Glc)-Tyr³-octreotate, which is considerably lower than for SiFA-Tyr³-octreotate (log P(ow) = 1.59). The initial in vivo evaluation of [¹?F]SiFA-Asn(AcNH-?-Glc)-PEG-Tyr³-octreotate revealed a significant uptake of radiotracer in the tumor tissue of AR42J tumor-bearing nude mice of 7.7% ID/g tissue weight. These results show that the high lipophilicity of the SiFA moiety can be compensated by applying hydrophilic moieties. Using this approach, a tumor-affine SiFA-containing peptide could successfully be used for receptor imaging for the first time in this proof of concept study.

Postoperative serum pro-calcitonin and C-reactive protein levels in patients with orthopedic infections

QUESTIONS UNDER STUDY / PRINCIPLES: The value of postoperative pro-calcitonin (PCT) in the follow-up of patients with localised infections in the orthopaedic domain is unknown.