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61.
Sachadyn P Jedrzejczak R Milewski S Kur J Borowski E 《Protein expression and purification》2000,19(3):343-349
The Candida albicans GFA1 gene encoding glucosamine-6-phosphate synthase, an enzyme of cell wall biosynthesis pathway in fungi and bacteria, recently an object of interest as a target for the chemotherapy of systemic mycoses, was PCR amplified and cloned to an Escherichia coli expression vector pET23b. The activity of the enzyme in the lysates from the overproducing E. coli strain was approximately 50-100 times higher than in the lysates from the control E. coli strain. This abundant overproduction allows to purify milligram amounts of the enzyme to homogeneity. 相似文献
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Cybulska B Gadomska I Mazerski J Borowski JGE Cheron M Bolard J 《Acta biochimica Polonica》2000,47(1):121-131
Rational chemical modification of amphotericin B (AMB) led to the synthesis of sterically hindered AMB derivatives. The selected optimal compound, N-methyl-N-D-fructosyl amphotericin B methyl ester (MF-AME) retains the broad spectrum of antifungal activity of the parent antibiotic, and exhibits a two orders of magnitude lower toxicity in vivo and in vitro against mammalian cells. Comparative studies of MF-AME and AMB comprising the determination of the spectroscopic properties of monomeric and self-associated forms of the antibiotics, the investigation of the influence of self-association on toxicity to human red blood cells, and of the antibiotic-sterol interaction were performed. On the basis of the results obtained it can be assumed that the improvement of the selective toxicity of MF-AME could in part be a consequence of the diminished concentration of water soluble oligomers in aqueous medium, and the better ability to differentiate between cholesterol and ergosterol. 相似文献
64.
Edward Borowski Zbyszek K. Blamowski Władysław Michałek 《Acta Physiologiae Plantarum》2000,22(3):271-274
The influence of triacontanol in a form of Tomatex preparation on basic indices of chlorophyll fluorescence in tomato leaves
(Delfina cv.), yield of fruits, and dry matter content in fruits was evaluated in a pot experiment situated in vegetation
hall in 1999. Tomatex was applied into roots at seedling stage (6–7 leaves) or at the stage of seedling and flowering of the
2nd inflorescence bunch. Plants were given by 0.3, 3.0, and 30 μg triacontanol per pot at a single dosage. Results obtained have
shown that triacontanol regardless of the dose applied, significantly increased the maximal efficiency of PSII photochemistry
in the dark (Fv/Fm), the efficiency of excitation capture by open PSII reaction centers (Fv’/Fm’), the actual quantum yield of PSII electron transport in the light-adapted state (ΦPSII), the photochemical quenching coefficient (Qp). However, nonphotochemical quenching coefficient (Qn) and non-radiative dissipation (NPQ) were decreased. Plants treated with triacontanol at the doses of 0.3 and 3.0 μg had
significantly higher yields of fruits than control. No differences were found between plants treated once and twice with the
growth regulator. Triacontanol did not show univocal effects on dry matter content in fruits either. 相似文献
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Basu A Yang K Wang M Liu S Chintala R Palm T Zhao H Peng P Wu D Zhang Z Hua J Hsieh MC Zhou J Petti G Li X Janjua A Mendez M Liu J Longley C Zhang Z Mehlig M Borowski V Viswanathan M Filpula D 《Bioconjugate chemistry》2006,17(3):618-630
Recombinant interferon-beta-1b (IFN-beta-1b) is used clinically in the treatment of multiple sclerosis. In common with many biological ligands, IFN-beta-1b exhibits a relatively short serum half-life, and bioavailability may be further diminished by neutralizing antibodies. While PEGylation is an approach commonly employed to increase the blood residency time of protein therapeutics, there is a further requisite for molecular engineering approaches to also address the stability, solubility, aggregation, immunogenicity and in vivo exposure of therapeutic proteins. We investigated these five parameters of recombinant human IFN-beta-1b in over 20 site-selective mono-PEGylated or multi-PEGylated IFN-beta-1b bioconjugates. Primary amines were modified by single or multiple attachments of poly(ethylene glycol), either site-specifically at the N-terminus, or randomly on the 11 lysines. In two alternate approaches, site-directed mutagenesis was independently employed in the construction of designed IFN-beta-1b variants containing either a single free cysteine or lysine for site-specific PEGylation. Optimization of conjugate preparation with 12 kDa, 20 kDa, 30 kDa, and 40 kDa amine-selective PEG polymers was achieved, and a comparison of the structural and functional properties of the IFN-beta-1b proteins and their PEGylated counterparts was conducted. Peptide mapping and MALDI-TOF mass spectrometric analysis confirmed the attachment sites of the PEG polymer. Independent biochemical and bioactivity analyses, including antiviral and antiproliferation bioassays, circular dichroism, capillary electrophoresis, flow cytometric profiling, reversed phase and size exclusion HPLC, and immunoassays demonstrated that the functional activities of the designed IFN-beta-1b conjugates were maintained, while the formation of soluble or insoluble aggregates of IFN-beta-1b was ameliorated. Immunogenicity and pharmacokinetic studies of selected PEGylated IFN-beta-1b compounds in mice and rats demonstrated both diminished IgG responses, and over 100-fold expanded AUC exposure relative to the unmodified protein. The results demonstrate the capacity of this macromolecular engineering strategy to address both pharmacological and formulation challenges for a highly hydrophobic, aggregation-prone protein. The properties of a lead mono-PEGylated candidate, 40 kDa PEG2-IFN-beta-1b, were further investigated in formulation optimization and biological studies. 相似文献
68.
Ujjinamatada RK Agasimundin YS Zhang P Hosmane RS Schuessler R Borowski P Kalicharran K Fattom A 《Nucleosides, nucleotides & nucleic acids》2005,24(10-12):1775-1788
The attempted synthesis of a ring-expanded guanosine (1) containing the imidazo[4,5-e][1,3]diazepine ring system by condensation of 1-(2'-deoxy-beta-D-erythropentofuranosyl)-4-ethoxycarbonylimidazole-5-carbaldehyde (2) with guanidine resulted in the formation of an unexpected product, 1-(2'-deoxy-beta-D-erythropentofuranosyl)-5-(2, 4-diamino-3, 6-dihydro-1,3, 5-triazin-6-yl)imidazole-4-carboxamide (7). The structure as well as the pathway of formation of 7 was corroborated by isolation of the intermediate, followed by its conversion to the product. Nucleoside 7 showed promising in vitro anti-helicase activity against the West Nile virus NTPase/helicase with an IC50 of 3-10 microg/mL. 相似文献
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70.
The mechanism of the oxidative cyclization reaction catalyzed by clavaminic acid synthase (CAS) was studied in silico. First, a classical molecular dynamics (MD) simulation was performed to obtain a realistic structure of the CAS-Fe(IV)=O-succinate-substrate complex; then potential of mean force (PMF) was calculated to assess the feasibility of the beta-lactam ring, more specifically its C4' corner, approaching the oxo atom. Based on the MD structure, a relatively large model of the active site region was selected and used in the B3LYP investigation of the reaction mechanism. The computational results suggest that once the oxoferryl species is formed, the oxidative cyclization catalyzed by CAS most likely involves either a mechanism involving C4'(S)-H bond cleavage of the monocyclic beta-lactam ring, or a biosynthetically unprecedented mechanism comprising (1) oxidation of the hydroxyl group of PCA to an O-radical, (2) retro-aldol-like decomposition of the O-radical to an aldehyde and a C-centered radical, which is stabilized by the captodative effect, (3) abstraction of a hydrogen atom from the C4'(S) position of the C-centered radical by the Fe(III)-OH species yielding an azomethine ylide, and (4) 1,3-dipolar cycloaddition to the ylide with aldehyde acting as a dipolarophile. Precedent for the new proposed mechanism comes from the reported synthesis of oxapenams via 1,3-dipolar cycloaddition reactions of aldehydes and ketones. 相似文献