Matches in SemOpenAlex for { <https://semopenalex.org/work/W1888661618> ?p ?o ?g. }
Showing items 1 to 75 of
75
with 100 items per page.
- W1888661618 abstract "To ensure that patients receive a safe and effective treatment, it is important to understand how drugs interact with and affect molecules within a cell. Here, evaluation of platinum based drugs and their ability to interfere with nucleic acid functions is presented. The main focus of this thesis has been to evaluate whether siRNA efficiency can be modified by two clinically used anticancer active platinum complexes; cisplatin and oxaliplatin. To evaluate the potency of platinum based drugs with respect to direct modulation of protein synthesis, siRNA methodology and protein silencing capacity in a luciferse based system was used. In addition to cellular based assays, platinated nucleic acids were characterized by thermal meting studies, HPLC, MALDI-MS, UPLC-ESI-MS and enzymatic and chemical probing resolved by PAGE. siRNA guide and/or passenger strands were pre-platinated and gel-purified prior to experimental evaluation. Platination of the siRNA passenger strand was found not to perturb the protein down regulation significantly. Platination of the siRNA guide strand on the other hand was found to decreases the protein down regulation capacity up to seven fold, when the platinum modification was located in non-seed regions. The effect was more pronounced for oxaliplatin. The thermal stability of RNA duplexes is reduced after platination. To evaluate if the observed platinum induced destabilization in the RNA environment was transferable to DNA, a thermal melting study was conducted. Analysis of the contributions from enthalpy and entropy to the free energy of duplex dissociation showed a larger variation in RNA. A study was also conducted to evaluate the DNA binding properties of novel platinum complexes/peptide chimeras. The platinum complexes contained a nonapeptide with either basic (lysine) or aliphatic (glycine, alanine) amino acids. The bulky peptide retarded the platinum binding to DNA, an effect that was counteracted by the electrostatic attraction of the positively charged lysine residues. Evaluation of the binding preference of cis-diamminedichloridoplatinum(II) (cisplatin) and dichloride [N,O-(L)-ornitine]platinum(II) (O-platin) to rRNA was performed by incubation of rRNA with the two complexes followed by enzymatic degradation and evaluation by HPLC and mass spectrometry. A guanosine preference over adenosine was confirmed for cisplatin and the opposite binding preference was observed for O-platin. We conclude that platinum drugs affect RNA function and can reduce siRNA efficiency." @default.
- W1888661618 created "2016-06-24" @default.
- W1888661618 creator A5080024842 @default.
- W1888661618 date "2011-01-01" @default.
- W1888661618 modified "2023-09-25" @default.
- W1888661618 title "Nucleic Acids as Drugs and Drug Targets With Focus on Anticancer Active Platinum Complexes and Small Interfering RNAs" @default.
- W1888661618 hasPublicationYear "2011" @default.
- W1888661618 type Work @default.
- W1888661618 sameAs 1888661618 @default.
- W1888661618 citedByCount "0" @default.
- W1888661618 crossrefType "dissertation" @default.
- W1888661618 hasAuthorship W1888661618A5080024842 @default.
- W1888661618 hasConcept C104317684 @default.
- W1888661618 hasConcept C121608353 @default.
- W1888661618 hasConcept C12554922 @default.
- W1888661618 hasConcept C161624437 @default.
- W1888661618 hasConcept C185592680 @default.
- W1888661618 hasConcept C21951064 @default.
- W1888661618 hasConcept C22615655 @default.
- W1888661618 hasConcept C24107716 @default.
- W1888661618 hasConcept C2776694085 @default.
- W1888661618 hasConcept C2778239845 @default.
- W1888661618 hasConcept C2780962732 @default.
- W1888661618 hasConcept C526805850 @default.
- W1888661618 hasConcept C54355233 @default.
- W1888661618 hasConcept C552990157 @default.
- W1888661618 hasConcept C55493867 @default.
- W1888661618 hasConcept C67705224 @default.
- W1888661618 hasConcept C86803240 @default.
- W1888661618 hasConcept C98274493 @default.
- W1888661618 hasConceptScore W1888661618C104317684 @default.
- W1888661618 hasConceptScore W1888661618C121608353 @default.
- W1888661618 hasConceptScore W1888661618C12554922 @default.
- W1888661618 hasConceptScore W1888661618C161624437 @default.
- W1888661618 hasConceptScore W1888661618C185592680 @default.
- W1888661618 hasConceptScore W1888661618C21951064 @default.
- W1888661618 hasConceptScore W1888661618C22615655 @default.
- W1888661618 hasConceptScore W1888661618C24107716 @default.
- W1888661618 hasConceptScore W1888661618C2776694085 @default.
- W1888661618 hasConceptScore W1888661618C2778239845 @default.
- W1888661618 hasConceptScore W1888661618C2780962732 @default.
- W1888661618 hasConceptScore W1888661618C526805850 @default.
- W1888661618 hasConceptScore W1888661618C54355233 @default.
- W1888661618 hasConceptScore W1888661618C552990157 @default.
- W1888661618 hasConceptScore W1888661618C55493867 @default.
- W1888661618 hasConceptScore W1888661618C67705224 @default.
- W1888661618 hasConceptScore W1888661618C86803240 @default.
- W1888661618 hasConceptScore W1888661618C98274493 @default.
- W1888661618 hasLocation W18886616181 @default.
- W1888661618 hasOpenAccess W1888661618 @default.
- W1888661618 hasPrimaryLocation W18886616181 @default.
- W1888661618 hasRelatedWork W1898166541 @default.
- W1888661618 hasRelatedWork W1975397475 @default.
- W1888661618 hasRelatedWork W1997537862 @default.
- W1888661618 hasRelatedWork W2019355650 @default.
- W1888661618 hasRelatedWork W204304389 @default.
- W1888661618 hasRelatedWork W2048397219 @default.
- W1888661618 hasRelatedWork W2068922188 @default.
- W1888661618 hasRelatedWork W2070957550 @default.
- W1888661618 hasRelatedWork W2085562285 @default.
- W1888661618 hasRelatedWork W2110490413 @default.
- W1888661618 hasRelatedWork W2114611012 @default.
- W1888661618 hasRelatedWork W2120231909 @default.
- W1888661618 hasRelatedWork W2123676174 @default.
- W1888661618 hasRelatedWork W2134559912 @default.
- W1888661618 hasRelatedWork W2182905597 @default.
- W1888661618 hasRelatedWork W2189270672 @default.
- W1888661618 hasRelatedWork W2510706524 @default.
- W1888661618 hasRelatedWork W2587161721 @default.
- W1888661618 hasRelatedWork W2745343149 @default.
- W1888661618 hasRelatedWork W2967233006 @default.
- W1888661618 isParatext "false" @default.
- W1888661618 isRetracted "false" @default.
- W1888661618 magId "1888661618" @default.
- W1888661618 workType "dissertation" @default.