Wyniki wyszukiwania - Biblioteka Nauki

1

Struktura i funkcja luliberyny

100%

Rzeszotarska B. , Kozlowska I.

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nr 3

2

Struktura tyreoglobuliny i jej funkcja w tarczycy

100%

Pawelczak K. , Rzeszotarska B.

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nr 4

3

Association of model peptides and dehydropeptides: N-acetyl-L-butyrine and [Z]-dehydrobutyrine N',N'-dimethylamides

100%

Broda M. A. , Rzeszotarska B.

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tom 53

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nr 1

EN

These comparative studies on the aggregation behaviour of Ac-(Z)-ΔAbu-NMe2 and Ac-L-Abu-NMe2 in carbon tetrachloride were performed by the analysis of their FTIR spectra and by theoretical calculations. The percentage of the monomeric form (α) decreased as concentration increased and this occurred to a higher degree for the (Z)-ΔAbu derivative than for its saturated analogue. The dimerization constant KD, calculated on the basis of the intensity of the monomer and associate bands in the νs(N-H) vibration region, is by three orders of magnitude larger for Ac-(Z)-ΔAbu-NMe2 than for Ac-L-Abu-NMe2. The obtained dimer geometries of the dehydro- compound were calculated by the B3LYP/6-31+G** method.

4

Porownanie wlasciwosci syntazy tymidylanowej oczyszczonej z tasiemca szczurzego, Hymenolepis diminuta, z wlasciwosciami enzymu zywiciela wyizolowanego z regenerujacej watraby szczura

70%

Ciesla J. , Machnicka B. , Pawelczak K. , Rzeszotarska B. , Rode W.

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nr 1-2

23-29

EN

Thymidylate synthases (TS) from the tapeworm, Hymenolepis diminuta, and regenerating rat liver have been purified by means of affinity chromatography on immobilized 10-formyl-5,8-dideazafolate and concentrated on immobilized p-aminophenyl-5-fluoro-2'-deoxyuridine monophosphate. Molecular weights of native TS from the tapeworm and regenerating rat liver were 62 kD and 81.5 kD, respectively, and molecular weights of the monomers were 34.4 kD and 34.9 kD, respectively, painting to dimeric structures of both enzymes. The dependence of TS activity on temperature (ARRHENIUS plot) was biphasic for the parasite enzyme, with lower activation energy above 32°C, and monophasic for the host enzyme. 2'-deoxyuridine-5'-monophosphate (dUMP) analogues, 5-fluoro-2'-deoxyuridine-5' -monophosphate (5-FdUMP), 2-tio-5-FdUMP, N⁴-hydroxy-2'-deoxycytidine-5'-monophosphate (N⁴-hydroxy-dCMP) and N⁴-hydroxy-5-FdCMP, were competitive with respect to dUMP, slow-binding inhibitors of TS from both sources, with K₁ values in 10⁻⁶ - 10⁻⁹ M range. 5-FdUMP was distinctly stronger inhibitor of the host than the tapeworm TS, whereas N⁴-hydroksy-5-FdCMP inhibited stronger the parasite enzyme. Interactions of 5,10-methylenetetrahydrofolate (CH₂H₄PteGlu) analogue, 10-propargyl-5,8-dideazafolate (pddPteGlu), and its di- and triglutamates with both enzymes were studied. Inhibition of the parasite and host enzymes by pddPteGlu was of mixed-type with respect to CH₂H₄PteGlu, with K₁ values in 10⁻⁸ M range. Introduction of additional glutamate residues changed inhibition type to noncompetitive with respect to CH₂H₄PteGlu and lowered K₁ values (pddPteGlu₃ < pddPteGlu₂ < pddPteGlu₁). The latter potentiation of inhibitory properties was distinctly stronger in case of the tapeworm than regenerating rat liver TS.

5

Conformational properties of N',N'-dimethylamides of N-acetyldehydroalanine and N-acetyl-[Z]-dehydrophenylalanine

70%

Siodlak D. , Broda M. A. , Rzeszotarska B. , Koziol A. E. , Dybala I.

Acta Biochimica Polonica

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2001

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tom 48

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nr 4

EN

Conformational preferences of Ac-ΔAla-NMe2 and Ac-(Z)-ΔPhe-NMe2 were studied and compared with those of their monomethyl counterparts as well as with those of their saturated analogues. X-Ray data and energy calculations revealed a highly conservative conformation of the dehydro dimethylamides, which is located in a high-energy region of the Ramachandran map.

6

Synthesis and biological activity of Na-[4-[N-[[3,4-dihydro-2-methyl-4-oxo-6-quinazolinyl]methyl]-N-propargylamino]phenylacetyl]-L-glutamic acid

51%

Kusakiewicz-Dawid A. , Bugaj M. , Dzik J. M. , Golos B. , Winska P. , Pawelczak K. , Rzeszotarska B. , Rode W.

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nr 1

EN

2-Deamino-2-methyl-N10-propargyl-5,8-dideazafolic acid (ICI 198583) is a potent inhibitor of thymidylate synthase. Its analogue, Nα-[4-[N-[(3,4-dihydro 2-methyl-4 -oxo- 6-quinazolinyl)methyl]-N-propargylamino]phenylacetyl]-L-glutamic acid, containing p-aminophenylacetic acid residue substituting p-aminobenzoic acid residue, was synthesized. The new analogue exhibited a moderately potent thymidylate synthase inhibition, of linear mixed type vs. the cofactor, N5,10 -methylenetetrahydrofolate. The K value of 0.34 uM, determined with a purified recombinant rat hepatoma enzyme, was about 30-fold higher than that reported for inhibition of thymidylate synthase from mouse leukemia L1210 cells by ICI 198583 (Hughes et al., 1990, J. Med. Chem. 33, 3060). Growth of mouse leukemia L5178Y cells was inhibited by the analogue (IC50 = 1.26 mM) 180-fold weaker than by ICI 198583 (IC50 = 6.9 uM).