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排序方式: 共有423条查询结果,搜索用时 15 毫秒
81.
Hideo Mukai Tetsuya Kimoto Yasushi Hojo Suguru Kawato Gen Murakami Shimpei Higo Yusuke Hatanaka Mari Ogiue-Ikeda 《Biochimica et Biophysica Acta (BBA)/General Subjects》2010
The hippocampus is a center for learning and memory as well as a target of Alzheimer's disease in aged humans. Synaptic modulation by estrogen is essential to understand the molecular mechanisms of estrogen replacement therapy. Because the local synthesis of estrogen occurs in the hippocampus of both sexes, in addition to the estrogen supply from the gonads, its functions are attracting much attention. 相似文献
82.
The main free amines identified during growth and development of rice seedlings were agmatine, putrescine, spermidine, diaminopropane and tyramine. Amine composition differed according to tissue and stages of development. Conjugated amines were only found in roots. We present evidence that arginine decarboxylase (ADC) regulates putrescine during the development of rice seedlings. When ADC action was blocked by DFMA (-DL-difluoromethylarginine, a specific irreversible inhibitor of ADC), polyamine titers and seedling development were diminished; when agmatine or putrescine was added, normal polyamine titers and growth were restored. The effects of DFMA were concentration dependent. DFMO (-DL-difluoromethylornithine, a specific irreversible inhibitor of ornithine decarboxylase or ODC) promoted growth and development at concentrations below 2 mM. This effect was probably related to its unexplained, but consistently observed slight enhancement of rice ADC. When the increase in the concentration of spermidine was prevented by CHA (cyclohexylammonium sulfate), the number of roots increased and the increase in length of leaves and roots was strongly inhibited. The addition of exogenous spermidine at the time of treatment with CHA reversed the inhibition by CHA.Abbreviations ADC
arginine decarboxylase
- ODC
ornithine decarboxylase
- DFMA
-DL-difluoromethylarginine
- DFMO
-DL-difluoromethylornithine
- CHA
cyclohexylammonium sulfate 相似文献
83.
Naidu S. Chowdari Chin Pan Chetana Rao David R. Langley Prasanna Sivaprakasam Bilal Sufi Daniel Derwin Yichong Wang Eilene Kwok David Passmore Vangipuram S. Rangan Shrikant Deshpande Pina Cardarelli Gregory Vite Sanjeev Gangwar 《Bioorganic & medicinal chemistry letters》2019,29(3):466-470
Uncialamycin analogs were evaluated as potential cytotoxic agents in an antibody-drug conjugate (ADC) approach to treating human cancer. These analogs were synthesized using Hauser annulations of substituted phthalides as a key step. A highly potent uncialamycin analog 3c with a valine-citrulline dipeptide linker was conjugated to an anti-mesothelin monoclonal antibody (mAb) through lysines to generate a meso-13 conjugate. This conjugate demonstrated subnanomolar potency (IC50?=?0.88?nM, H226 cell line) in in vitro cytotoxicity experiments with good immunological specificity to mesothelin-positive lung cancer cell lines. The potency and mechanism of action of this uncialamycin class of enediyne antitumor antibiotics make them attractive payloads in ADC-based cancer therapy. 相似文献
84.
Boron deficiency causes accumulation of chlorogenic acid and caffeoyl polyamine conjugates in tobacco leaves 总被引:5,自引:0,他引:5
Camacho-Cristóbal JJ Lunar L Lafont F Baumert A González-Fontes A 《Journal of plant physiology》2004,161(7):879-881
The effects of boron (B) deficiency on carbohydrate concentrations and the pattern of phenolic compounds were studied in leaves of tobacco plants (Nicotiana tabacum L.). Plants grown under B deficiency showed a notable increase in leaf carbohydrates and total phenolic compounds when compared to controls. The qualitative composition of phenolics was analyzed by HPLC-mass spectrometry. The level of caffeate conjugates (i.e., chlorogenic acid) increased in B-deficient plants. In addition, the accumulation of two caffeic acid amides (N-caffeoylputrescine and putative dicaffeoylspermidine) was observed. 相似文献
85.
抗体药物偶联物(antibody-drug conjugates,ADC)是一类由单克隆抗体和小分子细胞毒性药物通过连接子偶联而成的新型生物治疗药物。与传统的细胞毒药物相比,ADC具有靶向性强、毒副作用小等优势,在临床上展现较好的治疗潜力。其中,抗体部分通过与肿瘤细胞表面的靶向抗原结合,精准地将小分子细胞毒性药物递送至肿瘤部位,从而实现肿瘤特异性杀伤效果,是影响ADC疗效的核心要素之一。对近年来ADC药物中抗体的组成及其作用靶点的研究进展进行了综述。 相似文献
86.
《MABS-AUSTIN》2013,5(5):1190-1200
Conjugation of small molecule drugs to specific sites on the antibody molecule has been increasingly used for the generation of relatively homogenous preparations of antibody-drug conjugates (ADCs) with physicochemical properties similar or identical to those of the naked antibody. Previously a method for conjugation of small molecules to glycoproteins through existing glycans by using an engineered glycotransferase and a chemically reactive sugar as a handle was developed. Here, for the first time, we report the use of this method with some modifications to generate an ADC from a monoclonal antibody, m860, which we identified from a human naïve phage display Fab library by panning against the extracellular domain of human HER2. M860 bound to cell surface-associated HER2 with affinity comparable to that of Trastuzumab (Herceptin®), but to a different epitope. The m860ADC was generated by enzymatically adding a reactive keto-galactose to m860 using an engineered glycotransferase and conjugating the reactive m860 to aminooxy auristatin F. It exhibited potent and specific cell-killing activity against HER2 positive cancer cells, including trastuzumab-resistant breast cancer cells. This unique ADC may have utility as a potential therapeutic for HER2 positive cancers alone or in combination with other drugs. Our results also validate the keto-galactose/engineered glycotransferase method for generation of functional ADCs, which could potentially also be used for preparation of ADCs targeting other disease markers. 相似文献
87.
《Bioorganic & medicinal chemistry》2019,27(11):2187-2191
Targeted drug delivery platforms can increase the concentration of drugs in specific cell populations, reduce adverse effects, and hence improve the therapeutic effect of drugs. Herein, we designed two conjugates by installing the targeting ligand GalNAc (N-acetylgalactosamine) onto atorvastatin (AT). Compared to the parent drug, these two conjugates, termed G2-AT and G2-K-AT, showed increased hepatic cellular uptake. Moreover, both conjugates were able to release atorvastatin, and consequently showed dramatic inhibition of β-hydroxy-β-methylglutaryl-CoA (HMG-CoA) reductase and increased LDL receptors on cell surface. 相似文献
88.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1223-1225
Abstract We report here the synthesis and binding properties of oligonucleotides involving a perylene unit linked to the anomeric position of a 2′-deoxyribose residue. Both anomers were separated and incorporated separately at either the 5′-end or the internal position of a pyrimidine sequence. In any case the presence of the perylene unit stabilizes the complexes formed with either the single or the double-stranded target. 相似文献
89.
The effect of conjugation on antitumor activity of vindoline derivatives with octaarginine,a cell‐penetrating peptide 下载免费PDF全文
Zoltán Bánóczi András Keglevich Ildikó Szabó Ivan Ranđelović Zita Hegedüs Fruzsina L. Regenbach Péter Keglevich Zsófia Lengyel Viktor Háda Áron Szigetvári László Hazai József Tóvári Ferenc Hudecz 《Journal of peptide science》2018,24(10)
Some Vinca alkaloids (eg, vinblastine, vincristine) have been widely used as antitumor drugs for a long time. Unfortunately, vindoline, a main alkaloid component of Catharanthus roseus (L.) G. Don, itself, has no antitumor activity. In our novel research program, we have prepared and identified new vindoline derivatives with moderate cytostatic activity. Here, we describe the effect of conjugation of vindoline derivative with oligoarginine (tetra‐, hexa‐, or octapeptides) cell‐penetrating peptides on the cytostatic activity in vitro and in vivo. Br‐Vindoline‐(l )‐Trp‐OH attached to the N‐terminus of octaarginine was the most effective compound in vitro on HL‐60 cell line. Analysis of the in vitro activity of two isomer conjugates (Br‐vindoline‐(l )‐Trp‐Arg8 and Br‐vindoline‐(d )‐Trp‐Arg8 suggests the covalent attachment of the vindoline derivatives to octaarginine increased the antitumor activity significantly against P388 and C26 tumour cells in vitro. The cytostatic effect was dependent on the presence and configuration of Trp in the conjugate as well as on the cell line studied. The configuration of Trp notably influenced the activity on C26 and P388 cells: conjugate with (l )‐Trp was more active than conjugate with the (d )‐isomer. In contrast, conjugates had very similar effect on both the HL‐60 and MDA‐MB‐231 cells. In preliminary experiments, conjugate Br‐vindoline‐(l )‐Trp‐Arg8 exhibited some inhibitory effect on the tumor growth in P388 mouse leukemia tumor‐bearing mice. Our results indicate that the conjugation of modified vindoline could result in an effective compound even with in vivo antitumor activity. 相似文献
90.
A stable meta‐carborane enables the generation of boron‐rich peptide agonists targeting the ghrelin receptor 下载免费PDF全文
Dennis J. Worm Sylvia Els‐Heindl Martin Kellert Robert Kuhnert Stefan Saretz Johannes Koebberling Bernd Riedl Evamarie Hey‐Hawkins Annette G. Beck‐Sickinger 《Journal of peptide science》2018,24(10)
Boron neutron capture therapy (BNCT) is a binary cancer therapy, which combines the biochemical targeting of a boron‐containing drug with the regional localization of radiation treatment. Although the concept of BNCT has been known for decades, the selective delivery of boron into tumor cells remains challenging. G protein‐coupled receptors that are overexpressed on cancer cells in combination with peptidic ligands can be potentially used as shuttle system for a tumor‐directed boron uptake. In this study, we present the generation of short, boron‐rich peptide conjugates that target the ghrelin receptor. Expression of the ghrelin receptor on various cancer cells makes it a viable target for BNCT. We designed a novel hexapeptide super‐agonist that was modified with different specifically synthesized carborane monoclusters and tested for ghrelin receptor activation. A meta‐carborane building block with a mercaptoacetic acid linker was found to be optimal for peptide modification, owing to its chemical stability and a suitable activation efficacy of the conjugate. The versatility of this carborane for the development of peptidic boron delivery agents was further demonstrated by the generation of highly potent, boron‐loaded conjugates using the backbone of the known ghrelin receptor ligands growth hormone releasing peptide 6 and Ipamorelin. 相似文献