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111.
The construction of non-viral, virus-like vehicles for gene therapy involves the functionalization of multipartite constructs with nucleic acid-binding, cationic agents. Short basic peptides, alone or as fusion proteins, are appropriate DNA binding and condensing elements, whose incorporation into gene delivery vehicles results in the formation of protein–DNA complexes of appropriate size for cell internalization and intracellular trafficking. We review here the most used cationic peptides for artificial virus construction as well as the recently implemented strategies to control the architecture and biological activities of the resulting nanosized particles. 相似文献
112.
Yang Gao Jie Mi Chang‐Long Zhang Xiao‐Qing Zhang Ya‐Jie Peng He Bao Hai‐Long Zhang 《化学与生物多样性》2019,16(1)
Continually phytochemical study of the roots of Heracleum dissectum had led to the isolation of three previously undescribed polyacetylene glycosides ( 1 – 3 ), together with seven known compounds, including one polyacetylene ( 8 ) and six coumarins ( 4 – 7 and 9 – 10 ) using diverse chromatographic methods. The structures of these three new compounds were characterized and identified as deca‐4,6‐diyn‐1‐yl β‐d ‐glucopyranosyl‐(1→6)‐β‐d ‐glucopyranosyl‐(1→2)‐β‐d ‐glucopyranoside ( 1 ), (8Z)‐dec‐8‐ene‐4,6‐diyn‐1‐yl β‐d ‐glucopyranosyl‐(1→6)‐β‐d ‐glucopyranosyl‐(1→2)‐β‐d ‐glucopyranoside ( 2 ), and (8E)‐dec‐8‐ene‐4,6‐diyn‐1‐yl β‐d ‐glucopyranosyl‐(1→6)‐β‐d ‐glucopyranosyl‐(1→2)‐β‐d ‐glucopyranoside ( 3 ) based on their physicochemical properties and extensive analyses of various spectroscopic data. Their triglycerides accumulating activities were assayed and the results showed that the three new polyacetylene glycosides ( 1 – 3 ) exhibited triglyceride accumulating activities in 3T3‐L1 adipocytes. 相似文献
113.
Gholamhossein Sodeifian Fariba Razmimanesh 《Journal of biomolecular structure & dynamics》2019,37(7):1666-1684
In this research, for the first time, molecular dynamics (MD) method was used to simulate aspirin and ibuprofen at various concentrations and in neutral and charged states. Effects of the concentration (dosage), charge state, and existence of an integral protein in the membrane on the diffusion rate of drug molecules into lipid bilayer membrane were investigated on 11 systems, for which the parameters indicating diffusion rate and those affecting the rate were evaluated. Considering the diffusion rate, a suitable score was assigned to each system, based on which, analysis of variance (ANOVA) was performed. By calculating the effect size of the indicative parameters and total scores, an optimum system with the highest diffusion rate was determined. Consequently, diffusion rate controlling parameters were obtained: the drug–water hydrogen bond in protein-free systems and protein–drug hydrogen bond in the systems containing protein. 相似文献
114.
Around 10 million fatalities were recorded worldwide in 2020 due to cancer and statistical projections estimate the number to increase by 60% in 2040. With such a substantial rise in the global cancer burden, the disease will continue to impose a huge socio-economic burden on society. Currently, the most widely used clinical treatment modality is cytotoxic chemotherapy using platinum drugs which is used to treat variety of cancers. Despite its clinical success, critical challenges like resistance, off-target side effects and cancer variability often reduce its overall therapeutic efficiency. These challenges require faster diagnosis, simultaneous therapy and a more personalized approach toward cancer management. To this end, small-molecule ‘theranostic’ agents have presented a viable solution combining diagnosis and therapy into a single platform. In this review, we present a summary of recent efforts in the design and optimization of metal-based small-molecule ‘theranostic’ anticancer agents. Importantly, we highlight the advantages of a theranostic candidate over the purely therapeutic or diagnostic agent in terms of evaluation of its biological properties. 相似文献
115.
Y. Shechter M. Mironchik A. Saul E. Gershonov L. Precido-Patt K. Sasson H. Tsubery B. Mester A. Kapitkovsky S. Rubinraut Y. Vachutinski G. Fridkin M. Fridkin 《International journal of peptide research and therapeutics》2007,13(1-2):105-117
Most peptide and protein drugs are short-lived species in vivo with a circulatory half-life of several minutes. This is particularly valid for non-glycosylated proteins with a molecular
mass of less than 50 kDa. Since peptide/protein drugs are not absorbed orally, prolonged maintenance of therapeutically active
drugs in the circulatory system is of primary clinical importance. Another major obstacle of injected polypeptide drugs is
the elevated concentration of 100–1000 times above the therapeutical level that may be present in the circulatory system shortly
after administration. Such overdosing may lead to undesirable side effects such as over-stimulation or down-regulation of
receptor sites.
In this review we describe two new strategies that overcome these two problems of systemically injected peptide/protein drugs.
The first strategy includes Fmoc and FMS derivatization of peptides, proteins and low molecular-weight drugs, converting them
to inactive prodrugs that undergo reactivation with desirable pharmacokinetic patterns in body fluids. Based on this Fmoc/FMS-technology,
we have developed a second strategy, reversible pegylation. Inactive pegylated peptide/protein drugs release the native active
parental molecule at slow rates, and in homogeneous fashion under physiological conditions, thus facilitating prolonged therapeutic
effects, following a single administration. 相似文献
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Abstract Receptor-mediated stimulation of Dictyostelium cells by the aggregative chemoattractant cyclic AMP leads to a complex excitatory response resulting in chemotaxis and the synthesis and release of cyclic AMP as the relayed chemotactic signal. However, the mechanism of this stimulus-response coupling is not well understood. In this study, we show that a number of compounds, best known as inhibitors of cyclooxygenase activity in mammalian cells, prevent cyclic AMP receptor-mediated cell excitation and cyclic AMP accumulation in aggregation-competent Dictyostelium cells. These observations suggest that some eicosanoid-like compound(s) may be involved in stimulus-response coupling in this organism, as is the case in higher eukaryotic cells. 相似文献
120.
Yao Yu Menghan Yu Jian Liu Ning Ding Jiangmei Huang Dong Wan Yuliang Zhao Zhenhe Ma 《Journal of biophotonics》2019,12(11)
The objective of this study is to establish a novel method for continuously monitoring thrombus progression with various outcome measures and to assess the efficacy of antithrombotic drugs in murine thrombosis model in mice. In the study, thrombus was induced in the femoral vein of mice by FeCl3 and monitored over time by spectral‐domain optical coherence tomography (OCT). Three‐dimensional images of thrombi with or without heparin as an antithrombotic agent were obtained from OCT angiography. In addition, several parameters of thrombi were analyzed and compared between control and anticoagulant groups. By using OCT, we were able to trace thrombus generation in the same mouse in real time. We found that in our model heparin reduced thrombus size by ~60% and thrombus cross‐sectional area by 50%. OCT results also show that both time to thrombus size (>0.02mm3) and time to occlusion (>30%) were significantly reduced after heparin addition. This study demonstrates that OCT reliably monitors thrombus generation and progression from various aspects including thrombus size. This enables us to measure the kinetic of thrombosis more accurately, and effectively evaluate the efficacy and activities of antithrombotic drugs. This model may represent a useful tool in antithrombotic drug discoveries in preclinical studies. 相似文献