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1.
Cain G. D. and Bassow F. 1976. Porphyrins in the perienteric fluid of Ascaris lumbricoides. International Journal for Parasitology6: 79–82. Porphyrins in the perienteric fluid of adult female A. lumbricoides were esterified in methanolic H2SO4, extracted in chloroform, separated by thin-layer chromatography, and identified spectrophotometrically before and after conversion to their zinc and copper chelates. Protoporphyrin IX was the major component, comprising 95·4% of the total; the remaining 4·6 % was coproporphyrin III. Uroporphyrin was not detected; no porphyrins were recovered from other worm tissues. Fluid from worms with light and dark colored guts varied in protoporphyrin content from 0·58 to 4·08 nmoles/ml, respectively, but fluid from both groups contained similar molar ratios of protoporphyrin, coproporphyrin and heme. 相似文献
2.
Ashok Aspatwar Holger M. Becker Nanda Kumar Parvathaneni Milka Hammaren Aleksandra Svorjova Harlan Barker 《Journal of enzyme inhibition and medicinal chemistry》2018,33(1):1064-1073
Carbonic anhydrase (CA) IX is a hypoxia inducible enzyme that is highly expressed in solid tumours. Therefore, it has been considered as an anticancer target using specific chemical inhibitors. The nitroimidazoles DTP338 and DTP348 have been shown to inhibit CA IX in nanomolar range in vitro and reduce extracellular acidification in hypoxia, and impair tumour growth. We screened these compounds for toxicity using zebrafish embryos and measured their in vivo effects on human CA IX in Xenopus oocytes. In the toxicity screening, the LD50 for both compounds was 3.5?mM. Neither compound showed apparent toxicity below 300?µM concentration. Above this concentration, both compounds altered the movement of zebrafish larvae. The IC50 was 0.14?±?0.02?µM for DTP338 and 19.26?±?1.97?µM for DTP348, suggesting that these compounds efficiently inhibit CA IX in vivo. Our results suggest that these compounds can be developed as drugs for cancer therapy. 相似文献
3.
Zainab Saad Yusuf Tugba Kevser Uysal Ender Simsek Alessio Nocentini Sameh Mohamed Osman Claudiu T. Supuran
zen
zensoy Güler 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1340
Carbonic anhydrases (EC 4.2.1.1) catalyse the reversible hydration of CO2 into bicarbonate and protons. As a hypoxia-sensitive and tumour-associated isoform, isoform CA IX, is significantly overexpressed in various malignancies, being a validated target for new anticancer/antimetastatic drugs. A multitude of studies has shown that CA IX inhibition decreases cancer cell proliferation and metastasis through pHe/pHi modulation and enhancement of ferroptosis among others. Numerous studies demonstrated increased efficacy of cytotoxic drugs combined with CA inhibitors (CAIs) in various cancer types. We tested the inhibitory effect of boric acid (BA), an inorganic Lewis acid, on CA IX as well as other isoforms (CA I, II, and XII). BA acted as a millimolar in vitro CAI, decreased proliferation of two cancer cell lines, although not strong correlations between the in vitro inhibition and in vivo effects were observed. The mechanism of antiproliferative action of BA should be investigated in more detail. 相似文献
4.
Porphyrin depth in lipid bilayers as determined by iodide and parallax fluorescence quenching methods and its effect on photosensitizing efficiency 总被引:4,自引:0,他引:4 下载免费PDF全文
Bronshtein I Afri M Weitman H Frimer AA Smith KM Ehrenberg B 《Biophysical journal》2004,87(2):1155-1164
Photosensitization by porphyrins and other tetrapyrrole chromophores is used in biology and medicine to kill cells. This light-triggered generation of singlet oxygen is used to eradicate cancer cells in a process dubbed "photodynamic therapy," or PDT. Most photosensitizers are of amphiphilic character and they partition into cellular lipid membranes. The photodamage that they inflict to the host cell is mainly localized in membrane proteins. This photosensitized damage must occur in competition with the rapid diffusion of singlet oxygen through the lipid phase and its escape into the aqueous phase. In this article we show that the extent of damage can be modulated by employing modified hemato- and protoporphyrins, which have alkyl spacers of varying lengths between the tetrapyrrole ring and the carboxylate groups that are anchored at the lipid/water interface. The chromophore part of the molecule, and the point of generation of singlet oxygen, is thus located at a deeper position in the bilayer. The photosensitization efficiency was measured with 9,10-dimethylanthracene, a fluorescent chemical target for singlet oxygen. The vertical insertion of the sensitizers was assessed by two fluorescence-quenching techniques: by iodide ions that come from the aqueous phase; and by spin-probe-labeled phospholipids, that are incorporated into the bilayer, using the parallax method. These methods also show that temperature has a small effect on the depth when the membrane is in the liquid phase. However, when the bilayer undergoes a phase transition to the solid gel phase, the porphyrins are extruded toward the water interface as the temperature is lowered. These results, together with a previous publication in this journal, represent a unique and precedental case where the vertical location of a small molecule in a membrane has an effect on its membranal activity. 相似文献
5.
The complexes of horse myoglobin (Mb) with the anionic surfactant sodium dodecyl sulfate (SDS), and with the cationic surfactants cetyltrimethylammonium chloride (CTAC) and decyltrimethylammonium bromide (DeTAB), have been studied by a combination of surface tension measurements and optical spectroscopy, including heme absorption and aromatic amino acid fluorescence. SDS interacts in a monomeric form with Mb, which suggests the existence of a specific binding site for SDS, and induces the formation of a hexacoordinated Mb heme, possibly involving the distal histidine. Fluorescence spectra display an increase of tryptophan emission. Both effects point to an increased protein flexibility. SDS micelles induce both the appearance of two more heme species, one of which has the features of free heme, and protein unfolding. Mb/CTAC complexes display a very different behavior. CTAC monomers have no effect on the absorption spectra, and only a slight effect on the fluorescence spectra, whereas the formation of CTAC aggregates on the protein strongly affects both absorption and fluorescence. Mb/DeTAB complexes behave in a very similar way as Mb/CTAC complexes. The surface activity of the different Mb/surfactant complexes, as well as the interactions between the surfactants and Mb, are discussed on the basis of their structural properties. 相似文献
6.
Castelfranco PA 《Photosynthesis research》2007,91(1):25-36
Our research on chlorophyll biosynthesis, over a period of approximately twenty years, has been described, emphasizing those
areas in which our laboratory made significant and timely contributions. References to some of our most important articles
are included. Portions of the chlorophyll biosynthetic pathway, in which our own laboratory was not involved, for example,
the reduction of protochlorophyllide to chlorophyllide and the phytylation of the latter to yield chlorophyll a, have not been covered in this article. Those events which preceded my involvement with chlorophyll biosynthesis, but which
contributed to the formation of my own scientific personality, are mentioned briefly in the Introduction. My non-scientific
avocations have been included at the request of the reviewers and Govindjee. 相似文献
7.
Vatandoost J Zomorodipour A Sadeghizadeh M Aliyari R Bos MH Ataei F 《Biotechnology progress》2012,28(1):45-51
The Drosophila γ-glutamyl carboxylase (dγC) has substrate recognition properties similar to that of the vertebrate γ-carboxylase (γC), and its carboxylated product yield, in vitro, was shown to be more than that obtained with the human enzyme. However, whether the Drosophila enzyme is able to γ-carboxylate the human vitamin K-dependent (VKD) proteins, such as the human coagulation factor IX (hFIX), as synthesized in cultured Drosophila cells was not known. To examine this possibility, the Drosophila Schnider (S2) cell line was transfected with a metallothionein promoter-regulated hFIX-expressing plasmid. After induction with copper ion, expression efficiency of the active hFIX was analyzed by performing enzyme-linked immunosorbent assey (ELISA) and coagulation test on the culture supernatant of the transfected S2 cells during 72 h of postinduction. In comparison with Chinese hamster ovary cell line, S2 cells showed higher (≈ 12-fold) expression level of the hFIX. The γ-carboxylation of the Drosophila-derived hFIX was confirmed by evaluation of the expressed protein, after being precipitated with barium citrate. The biological activity of the S2 cell-derived hFIX indicated the capability of S2 cells to fulfill the required γ-carboxylation of the expressed hFIX. Coexpression of the human γ-glutamyl carboxylases (hγC) was also shown to improve both expression and γ-carboxylation of the hFIX. This is the first in vivo data to describe the ability of the dγC to recognize the human-based propeptide as substrate, which is an essential step for production of biologically active γ-carboxylated VKD proteins. 相似文献
8.
A unified multibranched chlorophyll (Chl) biosynthetic pathway is proposed. The proposed pathway takes into account the following
considerations: (a) that the earliest putative precursor of monovinyl Chl b that has been detected in higher plants is monovinyl
protochlorophyllide b, (b) that in most cases, Chl b biosynthesis has its roots in the Chl a biosynthetic pathway, (c) that
the Chl a biosynthetic pathway exhibits extensive biosynthetic heterogeneity, (d) that Chl biosynthesis may proceed differently
at different stages of greening and in different greening groups of plants. Integration of the Chl a and b biosynthetic pathways
into a unified multibranched pathway offers the functional flexibility to account for the structural and biosynthetic complexity
of photosynthetic membranes. In this context, it is proposed that the unified, multibranched Chl a/b biosynthetic pathway
represents the template of a Chl-protein biosynthesis center where photosystem (PS) 1, PS2, and light-harvesting Chl-protein
complexes are assembled into functional photosynthetic units. The individual biosynthetic routes or groups of two to three
adjacent biosynthetic routes may constitute Chl-protein biosynthesis subcenters, where specific Chl-protein complexes are
assembled.
This revised version was published online in September 2006 with corrections to the Cover Date. 相似文献
9.
Rajiv Kumar Vikas Sharma Silvia Bua 《Journal of enzyme inhibition and medicinal chemistry》2017,32(1):1187-1194
A library of benzenesulphonamides incorporating 1,2,3-triazole rings functionalised with ester, carboxylic acid, carboxamide, carboxyhydrazide, and hydroxymethyl moieties were synthesised. The carbonic anhydrase (CAs, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IV, and hCA IX. Among them, hCA II and IV are anti-glaucoma drug targets, being involved in aqueous humour secretion within the eye. hCA I was inhibited with Ki’s ranging between 8.3?nM and 0.8737?µM. hCA II, the physiologically dominant cytosolic isoform, was excellently inhibited by these compounds, with Ki’s in the range of 1.6–9.4?nM, whereas hCA IV was effectively inhibited by most of them, with Ki’s in the range of 1.4–55.3?nM. Thirteen of the twenty sulphonamides were found to be excellent inhibitors of tumour associated hCA IX with Ki’s?≤?9.5?nM. Many of the new compounds reported here showed low nM inhibitory action against hCA II, IV, and IX, isoforms involved in glaucoma and some tumours, making them interesting candidates for further medicinal chemistry/pharmacologic studies. 相似文献
10.
Steplewski A Brittingham R Jimenez SA Fertala A 《Biochemical and biophysical research communications》2005,335(3):749-755
The structural integrity of cartilage depends on the presence of extracellular matrices (ECM) formed by heterotypic fibrils composed of collagen II, collagen IX, and collagen XI. The formation of these fibrils depends on the site-specific binding between relatively small regions of interacting collagen molecules. Single amino acid substitutions in collagen II change the physicochemical and structural characteristics of those sites, thereby leading to an alteration of intermolecular collagen II/collagen IX interaction. Employing a biosensor to study interactions between R75C, R789C or G853E collagen II mutants and collagen IX, we demonstrated significant changes in the binding affinities. Moreover, analyses of computer models representing mutation sites defined exact changes in physicochemical characteristics of collagen II mutants. Our study shows that changes in collagen II/collagen IX affinity could represent one of the steps in a cascade of changes occurring in the ECM of cartilage as a result of single amino acid substitutions in collagen II. 相似文献