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Stability studies of monoclonal antibody nimotuzumab modified with chelator DTPA radiolabelled with lutetium-177 ([177Lu]Lu-hR3(p-SCN-Bn)DTPA)
Korec, David ; Kubíček, Vladimír (referee) ; Lázníčková, Alice (advisor)
Stability studies of monoclonal antibody nimotuzumab modified with chelator DTPA radiolabelled with lutetium-177 ([177Lu]Lu-hR3(p-SCN-Bn)DTPA) Diploma thesis David Korec Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry In this work was target to study the stability of monoclonal antibody Nimotuzumab, which was modified with chelator DTPA radiolabelled with radioactive Lutetium-177 ([177Lu] Lu-hR3 (p- SCN-Bn) DTPA). The radiochemical purity of the supplied antibody was 61%. For other uses had to purified. The chelator EDTA adds in addition for the labeled antibody. It has lower stability constant than the original chelating agent. He can catch the free ligand, which is excreted through the kidneys. For biodistribution studies is needed to ensure the highest purity that was well described by the distribution of radiopharmaceuticals in small bodies. Purification was used for gel permeation chromatography Sephadex. Purity was about 99%. HPLC analysis after one hour showed a small percentage of low molecular weight forms. It may be modified ligand with radionuclide or free radionuclide. At times long after purification the HPLC profile of low molecular weight fraction appeared in two peaks. They are therefore both options possible. The...
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Synthesis of Trichloroacetyl Esters of Aldols
Žáková, Lenka ; Jezberová, Michaela (referee) ; Kubíček, Vladimír (advisor)
This diploma thesis describes synthesis of trichloroacetyl esters of aldols which were obtained by a reaction of trichloroacetic acid with formaldehyde and another comercial aldehyde. Used were hydratopaldehyde, isobutyraldehyde, 2-methylpentanal, 2-ethylhexanal and 2-ethylbutanal. Some of these esters were described in the literature but only in part, several of them are new compounds. Excellent yields and clean products prove that the applied method is a good way to achieve these compounds that can be easily used for further processes.
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Observation of Stability of Glycine-NBDCl Derivative
Uhlářová, Tereza ; Jezberová, Michaela (referee) ; Kubíček, Vladimír (advisor)
OBSERVATION OF STABILITY OF GLYCINE-NBDCl DERIVATIVE Tereza Uhlářová Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Department of Biophysics and Physical Chemistry Diploma thesis 2010 Abstract The aim of this diploma thesis is monitoring of the chemical stability of derivative formed by glycine and fluorescent derivative, actually 7-chloro-4-nitrobenzo-2-oxa-1,3- diazole (NBD-Cl), under various conditions during approximately two months. As the obtained results show, the samples stored at laboratory temperature exhibit marked changes of concentrations of both the derivative itself and a by-product. An influence of light seems to be less important at the laboratory temperature. For the samples stored cooled (2 žC) in dark the changes in both concentrations were observed to be significantly diminished compared to the samples stored at the laboratory temperature. Based on the all performed experiments the conclusion is that regardless of the storage conditions the chemical stabilization of the samples is necessary.
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Synthesis of 2,2'-bipyridine and 1,10-phenantroline derivatives containing sugars molecules
Dušková, Kateřina ; Jezberová, Michaela (referee) ; Kubíček, Vladimír (advisor)
Kateřina Dušková Alcalá de Henares, 2008/2009 SYNTÉZA DERIVÁTŮ 2,2'-BIPYRIDINU A 1,10-FENANTROLINU OBSAHUJÍCÍCH MOLEKULY CUKRŮ ABSTRAKT Tato diplomová práce popisuje přípravu O-glykosidu a N-glykosidů s deriváty 1,10- fenantrolinu a 2,2'-bipyridinu, obsahujících molekuly monosacharidů ze série D-gluko, galakto a manopyranosa a L-fuco a ramnopyranosa. Syntéza glykosylaminů byla prováděna přímými reakcemi mezi monosacharidy a aminy za různých podmínek reakce s cílem optimalizovat proces v souladu s literárními zdroji. Dále pak zachycuje syntézu 5- hydroxymethyl-5'-methyl-2,2'-bipyridinu a následně pokus o přípravu O-glykosidu z alkoholu bipyridinu a monosacharidu s chráněnými -OH skupinami.
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Spectral Properties of Benzimidazoles
Lukešová, Marie ; Jezberová, Michaela (referee) ; Kubíček, Vladimír (advisor)
Spectral Properties of Benzimidazoles Marie Lukešová Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biophysics and Physical Chemistry Abstract: This diploma thesis deals with the spectral properties of benzimidazoles. Most of benzimidazoles are anthelmintic active drug, used primarily in veterinary medicine. Some substances are used as fungicides. The main aim of this study was to clarify the influence of solvents on the absorption spectra and especially on the fluorescence of benzimidazoles. The influence of aprotic and protic solvent, the influence of polarity of solvent and the influence of pH of solvents were studied. The thesis includes two parts: theoretical and practical. In the theoretical part physicochemical properties of benzimidazoles, benzimidazoles possibility of detection, UV-VIS and fluorescence spectrophotometry are summarized. In the practical part results of the measurement are processed into tables and graphs. It was found that the influence of solvent depends on the structure of the substance. Therefore it is necessary to check each substance separately.
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Establishment of CD method for studies of amyloid-oligomerization process during Alzheimer disease
Vilímová, Jana ; Kubíček, Vladimír (referee) ; Lázníčková, Alice (advisor)
One of the main features of Alzheimer's disease (AD) are senile plaques in the brain. They are composed of β-amyloid (Aβ) peptides, which oligomerize and form fibrils during pathological conditions. Inhibition of this oligomerization process is believed to be a possible therapy to prevent the progression of AD. Circular dichroism (CD) spectrometry is an optical method which enables to follow changes in the secondary structures of proteins. Within this study a CD-method was established by which the oligomerization process of synthetic Aβ 42 was monitored. During the validation of the method several parameters as the influence of several organic solvents as Ethanol, Methanol and DMSO on the spectra and the solvent solution and concentration of Aβ 42 were assessed. Then it was investigated if the addition of proposed disintegrating substances (natural compound, fluorescence dyes and antibiotics) resulted in a delayed onset of the oligomerization process of Aβ 42. Since these substances were dissolved in different solvents, the possible effects of the solvents alone as appropriate blank values were also carried out. The oligomerization experiments were carried out at 37 řC and CD-spectra were recorded at several time points (0, 7, 24, 48 hours). In general, resulted CD-spectra showed concentration...
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Study of radiolabelling of hyaluronic acid by oxidative iodination
Dvořáčková, Eliška ; Lázníčková, Alice (advisor) ; Kubíček, Vladimír (referee)
Study of radiolabelling of hyaluronic acid by oxidative iodination Diploma paper Eliška Dvořáčková 2009 Charles University in Prague, Pharmaceutical Faculty in Hradec Králové Department of biophysics and physical chemistry In the frame of this work the literature describing characteristics and possible applications of hyaluronic acid and methods of radiolabelling of compounds with a view to the radioiodination was read up. In experimental part of the task two methods of oxidative iodination of hyaluronic acid modified by tyramine with the lowest degree of modification ( HA - TM - 1 ) was examined. Chloramine method, used as first one, turned out ineligible as due to presence of oxidative agent in the phase with hyaluronic acid a partial degradation of the sequence occurred. Another method of iodination with the use of iodogen is heterogenous reaction, oxidative agent is present as an insoluble deposit on the walls of the reaction vial. This method of radiolabelling was more moderate to hyaluronic acid. The reaction was interrupted by applying the reaction system on the column with Sephadex G - 50 wherby the labelled compound was separated from the aggressive reactive environment. It turned out that this way of refinement of the labelled product does not eliminate the rests of the radioactive iodide....
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Stability studies of monoclonal antibody nimotuzumab modified with chelator DOTA radiolabelled with lutetium-177 ([177Lu]Lu-hR3(p-SCN-Bn)DOTA)
Petřík, Michal ; Lázníčková, Alice (advisor) ; Kubíček, Vladimír (referee)
The higher expressivity of the gene for the receptor of epidermal growth factor (EGF) and consequently higher number of receptors (EGFR) on the surface of cells is closely linked with the tumour proliferation of these cells and with poor prognosis for patients. For such reason the EGFR became one of the main objectives in the therapy of tumours. Nimotuzumab (also known as h-R3) is humanized monoclonal antibody which blocks receptor for epidermal growth factor. The object of this thesis was to determinate radiochemical purity of this antibody conjugated with bifunctional chelator DOTA and marked by luthecium, possibly purification of this antibody and consequently determination of its stability in different environments. In acetate buffer pH = 7, in an environment of the surplus of competitive ligand EDTA and in plasma of rats. Adequate analytic methods were used for these tasks: high-efficiency liquid chromatography, gel permeation chromatography and chromatography on thin layer. The results of the thesis demonstrated that this way of modification for further radiolabelling is not appropriate for large protein structures such as Nimotuzumab
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Quantitative binding of different analogues of vancomycine to D-Ala-D-Ala using surface plasmon resonance
Černá, Ivana ; Szotáková, Barbora (advisor) ; Kubíček, Vladimír (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Ivana Černá Consultant: Drª María José Hernáiz Gómez-Dégano Doc. Ing. Barbora Szotáková, PhD. Title: Quantitative binding of different analogues of vancomycine to D-Ala-D-Ala using surface plasmon resonance This diploma thesis discusses the interaction studies of different glycopeptide antibiotics: teicoplanin; MDL 63,246; mideplanin; BI 397 (dalbavancin); A 40926 and vancomycin with D-Ala-D-Ala dipeptide. Firstly, the HPLC analysis conditions for these antibiotics were defined and optimized in order to probe their purity. Then, the interaction studies were carried out, for that various self-assembled monolayers (SAM) were prepared based on different hydrophobicity and length of the chain. These SAMs were functionalized with the dipeptide D-Ala-D-Ala for the study of the binding with the antibiotics. The results suggest that the best way to prepare the SAM is incubation of the chip overnight in the ethanol solution of alcanothiol chain. The most applicable SAM for the study of interaction of antibiotic to D-Ala-D-Ala is formed by alcanothiol chain with a carbon chain of 8 carbons and a tetraethylene glycol chain ending in a carboxylic group. Over this surface we performed the study of...
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