We studied sequence-dependent retention properties of synthetic 5'-terminal phosphate absent trinucleotides containing adenine, guanine and thymine through reversed-phase liquid chromatography (RPLC) and QSRR modelling. We investigated the influence of separation conditions, namely mobile phase composition (ion interaction agent content, pH and organic constituent content), on sequence-dependent separation by means of ion-interaction RPLC (II-RPLC) using two types of models: experimental design-artificial neural networks (ED-ANN), and linear regression based on molecular dynamics data. The aim was to determine those properties of the above-mentioned analytes responsible for the retention dependence of the sequence. Our results show that there is a deterministic relation between sequence and II-RPLC retention properties of the studied trinucleotides. Further, we can conclude that the higher the content of ion-interaction agent in the mobile phase, the more prominent these properties are. We also show that if we approximate the polar component of solvation energy in QSRR by the electrostatic work in transferring molecules from vacuum to water, and the non-polar component by the solvent accessible surface area, these parameters best describe the retention properties of trinucleotides. There are some exceptions to this finding, namely sequences 5'-NAN-3', 5'-ANN-3', 5'-TGN-3', 5'-NTA-3'and 5'-NGA-3' (N stands for generic nucleotide). Their role is still unknown, but since linear regression including these specific constellations showed a higher observable variance coverage than the model with only the basic descriptors, we may assume that solvent-analyte interactions are responsible for the exceptional behaviour of 5'-NAN-3' & 5'-ANN-3' trinucleotides and some intramolecular interactions of neighbouring nucleobases for 5'-TGN-3', 5'-NTA-3'and 5'-NGA-3' trinucleotides.
- MeSH
- adenin analogy a deriváty izolace a purifikace MeSH
- chromatografie s reverzní fází MeSH
- guanin analogy a deriváty izolace a purifikace MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- neuronové sítě (počítačové) MeSH
- oligonukleotidy izolace a purifikace MeSH
- rozpouštědla MeSH
- simulace molekulární dynamiky MeSH
- statická elektřina MeSH
- thymin analogy a deriváty izolace a purifikace MeSH
- voda MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Publikační typ
- časopisecké články MeSH
A series of new monophosphates of 1-[2-(phosphonomethoxy)alkyl]thymines, such as PMPTp(,) 3-MeO-PMPTp, HPMPTp, and FPMPTp, were synthesized and tested for their ability to inhibit human thymidine phosphorylase. Kinetic measurements of enzyme activity were performed using thymidine and inorganic phosphate as the substrates. The data show that some monophosphates provide a considerable increase of the multisubstrate inhibitory effect. The highest inhibitory potency was found with (R)-FPMPTp 4c (K (i) (dT) = 4.09 ± 0.47 μM, K (i)(P(i)) = 2.13 ± 0.29 μM) and (R) 3-MeO-PMPTp 4d (K (i) (dT) = 5.78 ± 0.71 μM, K (i)(P(i)) = 2.71 ± 0.37 μM).
- MeSH
- Cricetulus MeSH
- fosfáty MeSH
- fosforylace MeSH
- kinetika MeSH
- křečci praví MeSH
- kyseliny fosforité chemická syntéza chemie metabolismus farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- thymidin MeSH
- thymidinfosforylasa antagonisté a inhibitory MeSH
- thymin analogy a deriváty chemická syntéza chemie metabolismus farmakologie MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
A series of N(3)-substituted thymine acyclic nucleoside phosphonates bearing a number of (phosphonomethoxy)alkyl groups were synthesized and investigated for their ability to inhibit the human thymidine phosphorylase expressed in V79 Chinese hamster cells, as well as thymidine phosphorylase from SD-lymphoma, Escherichia coli and human placenta. In comparison to N(1)- substituted analogues which possess a considerable inhibitory activity towards thymidine phosphorylase from SD-lymphoma, the results showed a marginal inhibitory effect of these compounds. None of the presented N(3)-substituted derivatives possess a significant cytostatic activity.
- MeSH
- Cricetulus MeSH
- financování organizované MeSH
- inhibitory enzymů farmakologie chemická syntéza MeSH
- křečci praví MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- lymfom T-buněčný enzymologie MeSH
- organofosfonáty farmakologie chemická syntéza MeSH
- placenta enzymologie MeSH
- pyrimidinové nukleosidy farmakologie chemická syntéza MeSH
- thymidinfosforylasa antagonisté a inhibitory MeSH
- thymin analogy a deriváty farmakologie chemická syntéza MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
Various methods were used in the syntheses of a number of pyrimidine acyclic nucleoside phosphonates and their derivatives such as a nucleophilic fluorination, Suzuki-Miyaura coupling reactions and phosphorylation. These new compounds were further investigated for their potential biological activity. Based on results obtained the ability to inhibit human thymidine phosphorylase some of them was found.
- MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- fosforylace MeSH
- inhibitory enzymů chemická syntéza chemie farmakologie MeSH
- kyseliny fosforité chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- thymidinfosforylasa antagonisté a inhibitory MeSH
- thymin analogy a deriváty chemická syntéza chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Základní ideou hybridního zobrazení PET/CT je integrace morfologického a metabolického zobrazení. Součástí skeneru je spojená gantry CT subsystému a PET systému, která umožňuje souosou akvizici dat PET i CT. Požadavek spojení pozitronové výpočetní tomografie (PET) a výpočetní tomografie (CT) vznikl především z důvodu nízkého prostorového rozlišení pozitronové emisní tomografie. Metabolická informace získaná na molekulární úrovni podstatně obohacuje také CT vyšetření.
- MeSH
- financování organizované MeSH
- fluorodeoxyglukosa F18 diagnostické užití MeSH
- nádory diagnóza radiografie MeSH
- ošetřovatelská péče metody MeSH
- počítačová rentgenová tomografie metody využití MeSH
- pozitronová emisní tomografie metody využití MeSH
- radiofarmaka klasifikace terapeutické užití MeSH
- radionuklidy diagnostické užití MeSH
- thymin analogy a deriváty diagnostické užití MeSH
