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Igor Zelezetsky 《生物化学与生物物理学报:生物膜》2006,1758(9):1436-1449
An important class of cytolytic antimicrobial peptides (AMPs) assumes an amphipathic, α-helical conformation that permits efficient interaction with biological membranes. Host defence peptides of this type are widespread in nature, and numerous synthetic model AMPs have been derived from these or designed de novo based on their characteristics. In this review we provide an overview of the ‘sequence template’ approach which we have used to design potent artificial helical AMPs, to guide structure-activity relationship studies aimed at their optimization, and to help identify novel natural AMP sequences. Combining this approach with the rational use of natural and non-proteinogenic amino acid building blocks has allowed us to probe the individual effects on the peptides' activity of structural and physico-chemical parameters such as the size, propensity for helical structuring, amphipathic hydrophobicity, cationicity, and hydrophobic or polar sector characteristics. These studies furthermore provided useful insights into alternative modes of action for natural membrane-active helical peptides. 相似文献
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Elina Tzvetanova Almira Pavlova Albena Alexandrova Galina Nenkova Lubomir Petrov Margarita Kirkova Radoslav Girchev Emilia Naydenova 《Cell biochemistry and function》2009,27(4):243-250
In‐vivo effects of nociceptin (N/OFQ(1‐13)NH2) on the levels of lipid peroxidation and cell enzyme (superoxide dismutase, glutathione peroxidase and glutathione reductase) and non‐enzyme (glutathione) antioxidants in brain of control and kainic acid‐treated rats were studied. N/OFQ(1‐13)NH2 effects were compared with those of its structural analogue [Orn9]N/OFQ(1‐13)NH2. Kainic acid (25 µg, i.c.v) increased the lipid peroxidation (4 and 24 h after kainic acid treatment) and decreased the glutathione level (1 h after kainic acid injection). We failed to find, any changes in antioxidant enzyme activities, independently of the time of kainic acid treatment. At the background of kainic acid‐effects, N/OFQ(1‐13)NH2 and [Orn9] N/OFQ(1‐13)NH2, injected 30 min before kainic acid, had no effects on all parameters, tested in brain. In addition, the neuropeptides did not change the antioxidant status in brain of control animals. It might be concluded that N/OFQ(1‐13)NH2 and [Orn9]N/OFQ(1‐13)NH2 have neither pro‐ nor anti‐oxidant activity. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
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Aviran Amir Amit Hetsron Shimon Shatzmiller Gary Gellerman 《International journal of peptide research and therapeutics》2009,15(3):241-246
Peptide nucleic acid (PNA) is a DNA analog able to form hybridization complexes with complementary DNA or RNA strands. Many
PNAs have been described in recent years, particularly chiral PNA analogs. Chiral heteronucleotide ONA (Orn backbone PNA)
is an important tool in the antisensing field, but was not been fully explored yet. In the present work, we performed studies
toward the synthesis of chiral heteronucleotide ONA sequences by utilizing a Fmoc/Boc-based submonomer approach on solid support.
The desired oligomers with different nucleic content and length were obtained in very good yields and high purity. Specific
binding to the complimentary ssDNA oligomers was demonstrated. 相似文献
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Karin Terburgh Zander Lindeque Shayne Mason Francois van der Westhuizen Roan Louw 《生物化学与生物物理学报:疾病的分子基础》2019,1865(1):98-106
Leigh syndrome is one of the most common childhood-onset neurometabolic disorders resulting from a primary oxidative phosphorylation dysfunction and affecting mostly brain tissues. Ndufs4?/? mice have been widely used to study the neurological responses in this syndrome, however the reason why these animals do not display strong muscle involvement remains elusive. We combined biochemical strategies and multi-platform metabolomics to gain insight into the metabolism of both glycolytic (white quadriceps) and oxidative (soleus) skeletal muscles from Ndufs4?/? mice. Enzyme assays confirmed severely reduced (80%) CI activity in both Ndufs4?/? muscle types, compared to WTs. No significant alterations were evident in other respiratory chain enzyme activities; however, Ndufs4?/? solei displayed moderate decreases in citrate synthase (12%) and CIII (18%) activities. Through hypothesis-generating metabolic profiling, we provide the first evidence of adaptive responses to CI dysfunction involving non-classical pathways fueling the ubiquinone (Q) cycle. We report a respective 48 and 34 discriminatory metabolites between Ndufs4?/? and WT white quadriceps and soleus muscles, among which the most prominent alterations indicate the involvement of the glycerol-3-phosphate shuttle, electron transfer flavoprotein system, CII, and proline cycle in fueling the Q cycle. By restoring the electron flux to CIII via the Q cycle, these adaptive mechanisms could maintain adequate oxidative ATP production, despite CI deficiency. Taken together, our results shed light on the underlying pathogenic mechanisms of CI dysfunction in skeletal muscle. Upon further investigation, these pathways could provide novel targets for therapeutic intervention in CI deficiency and potentially lead to the development of new treatment strategies. 相似文献
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The rat GPRC6A: cloning and characterization 总被引:2,自引:0,他引:2
Wellendorph P Burhenne N Christiansen B Walter B Schmale H Bräuner-Osborne H 《Gene》2007,396(2):257-267
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Justin E. Jones 《Bioorganic chemistry》2010,38(2):62-1135
Helicobacter pylori encodes a potential virulence factor, agmatine deiminase (HpAgD), which catalyzes the conversion of agmatine to N-carbamoyl putrescine (NCP) and ammonia - agmatine is decarboxylated arginine. Agmatine is an endogenous human cell signaling molecule that triggers the innate immune response in humans. Unlike H. pylori, humans do not encode an AgD; it is hypothesized that inhibition of this enzyme would increase the levels of agmatine, and thereby enhance the innate immune response. Taken together, these facts suggest that HpAgD is a potential drug target. Herein we describe the optimized expression, isolation, and purification of HpAgD (10-30 mg/L media). The initial kinetic characterization of this enzyme has also been performed. Additionally, the crystal structure of wild-type HpAgD has been determined at 2.1 Å resolution. This structure provides a molecular basis for the preferential deimination of agmatine, and identifies Asp198 as a key residue responsible for agmatine recognition, which has been confirmed experimentally. Information gathered from these studies led to the development and characterization of a novel class of haloacetamidine-based HpAgD inactivators. These compounds are the most potent AgD inhibitors ever described. 相似文献
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