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901.
Modulation of angiogenesis by a tetrameric tripeptide that antagonizes vascular endothelial growth factor receptor 1 总被引:1,自引:0,他引:1
Ponticelli S Marasco D Tarallo V Albuquerque RJ Mitola S Takeda A Stassen JM Presta M Ambati J Ruvo M De Falco S 《The Journal of biological chemistry》2008,283(49):34250-34259
Vascular endothelial growth factor receptor-1 (VEGFR-1, also known as Flt-1) is involved in complex biological processes often associated to severe pathological conditions like cancer, inflammation, and metastasis formation. Consequently, the search for antagonists of Flt-1 has recently gained a growing interest. Here we report the identification of a tetrameric tripeptide from a combinatorial peptide library built using non-natural amino acids, which binds Flt-1 and inhibits in vitro its interaction with placental growth factor (PlGF) and vascular endothelial growth factor (VEGF) A and B (IC(50) approximately 10 microm). The peptide is stable in serum for 7 days and prevents both Flt-1 phosphorylation and the capillary-like tube formation of human primary endothelial cells stimulated by PlGF or VEGF-A. Conversely, the identified peptide does not interfere in VEGF-induced VEGFR-2 activation. In vivo, this peptide inhibits VEGF-A- and PlGF-induced neoangiogenesis in the chicken embryo chorioallantoic membrane assay. In contrast, in the cornea, where avascularity is maintained by high levels of expression of the soluble form of Flt-1 receptor (sFlt-1) that prevents the VEGF-A activity, the peptide is able to stimulate corneal mouse neovascularization in physiological condition, as reported previously for others neutralizing anti-Flt-1 molecules. This tetrameric tripeptide represents a new, promising compound for therapeutic approaches in pathologies where Flt-1 activation plays a crucial role. 相似文献
902.
Cristiana Castaldo Valeria Vastano Rosa Anna Siciliano Marco Candela Manuela Vici Lidia Muscariello Rosangela Marasco Margherita Sacco 《Microbial cell factories》2009,8(1):14-10
Background
Lactic acid bacteria of the genus Lactobacillus and Bifidobacterium are one of the most important health promoting groups of the human intestinal microbiota. Their protective role within the gut consists in out competing invading pathogens for ecological niches and metabolic substrates. Among the features necessary to provide health benefits, commensal microorganisms must have the ability to adhere to human intestinal cells and consequently to colonize the gut. Studies on mechanisms mediating adhesion of lactobacilli to human intestinal cells showed that factors involved in the interaction vary mostly among different species and strains, mainly regarding interaction between bacterial adhesins and extracellular matrix or mucus proteins. We have investigated the adhesive properties of Lactobacillus plantarum, a member of the human microbiota of healthy individuals. 相似文献903.
Guglielmo Vesco Marco Lamperti Domenico Salerno Claudia Adriana Marrano Valeria Cassina Riccardo Rigo Enrico Buglione Maria Bondani Giulia Nicoletto Francesco Mantegazza Claudia Sissi Luca Nardo 《Nucleic acids research》2021,49(17):9724
G-quadruplexes embedded within promoters play a crucial role in regulating the gene expression. KIT is a widely studied oncogene, whose promoter contains three G-quadruplex forming sequences, c-kit1, c-kit2 and c-kit*. For these sequences available studies cover ensemble and single-molecule analyses, although for kit* the latter were limited to a study on a promoter domain comprising all of them. Recently, c-kit2 has been reported to fold according to a multi-step process involving folding intermediates. Here, by exploiting fluorescence resonance energy transfer, both in ensemble and at the single molecule level, we investigated the folding of expressly designed constructs in which, alike in the physiological context, either c-kit2 or c-kit* are flanked by double stranded DNA segments. To assess whether the presence of flanking ends at the borders of the G-quadruplex affects the folding, we studied under the same protocols oligonucleotides corresponding to the minimal G-quadruplex forming sequences. Data suggest that addition of flanking ends results in biasing both the final equilibrium state and the folding kinetics. A previously unconsidered aspect is thereby unravelled, which ought to be taken into account to achieve a deeper insight of the complex relationships underlying the fine tuning of the gene-regulatory properties of these fascinating DNA structures. 相似文献
904.
905.
906.
Identification of mutations causing temperature-sensitive defects in Semliki Forest virus RNA synthesis 总被引:1,自引:1,他引:0 下载免费PDF全文
We have sequenced the nonstructural protein coding region of Semliki Forest virus temperature-sensitive (ts) mutant strains ts1, ts6, ts9, ts10, ts11, ts13, and ts14. In each case, the individual amino acid changes uncovered were transferred to the prototype strain background and thereby identified as the underlying cause of the altered RNA synthesis phenotype. All mutations mapping to the protease domain of nonstructural protein nsP2 caused defects in nonstructural polyprotein processing and subgenomic RNA synthesis, and all mutations in the helicase domain of nsP2 affected subgenomic RNA production. These types of defects were not associated with mutations in other nonstructural proteins. 相似文献
907.
Topological patterns in the development and evolution of metazoa, from sponges to chordates, are considered by means of previously
elaborated methodology, with the genus of the surface used as a topological invariant. By this means metazoan morphogenesis
may be represented as topological modification(s) of the epithelial surfaces of an animal body. The animal body surface is
an interface between an organism and its environment, and topological transformations of the body surface during metazoan
development and evolution results in better distribution of flows to and from the external medium, regarded as the source
of nutrients and oxygen and the sink of excreta, so ensuring greater metabolic intensity. In sponges and some Cnidaria, the
increase of this genus up to high values and the shaping of topologically complicated fractal-like systems are evident. In
most Bilateria, a stable topological pattern with a through digestive tube is formed, and the subsequent topological complications
of other systems can also appear. The present paper provides a topological interpretation of some developmental events through
the use of well-known mathematical concepts and theorems; the relationship between local and global orders in metazoan development,
i.e., between local morphogenetic processes and integral developmental patterns, is established. Thus, this methodology reveals
a “topological imperative”: A certain set of topological rules that constrains and directs biological morphogenesis. 相似文献
908.
SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity 总被引:23,自引:0,他引:23
Mammalian target of rapamycin (mTOR) controls cell growth and proliferation via the raptor-mTOR (TORC1) and rictor-mTOR (TORC2) protein complexes. Recent biochemical studies suggested that TORC2 is the elusive PDK2 for Akt/PKB Ser473 phosphorylation in the hydrophobic motif. Phosphorylation at Ser473, along with Thr308 of its activation loop, is deemed necessary for Akt function, although the regulatory mechanisms and physiological importance of each phosphorylation site remain to be fully understood. Here, we report that SIN1/MIP1 is an essential TORC2/PDK2 subunit. Genetic ablation of sin1 abolished Akt-Ser473 phosphorylation and disrupted rictor-mTOR interaction but maintained Thr308 phosphorylation. Surprisingly, defective Ser473 phosphorylation affected only a subset of Akt targets in vivo, including FoxO1/3a, while other Akt targets, TSC2 and GSK3, and the TORC1 effectors, S6K and 4E-BP1, were unaffected. Our findings reveal that the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2 function in cell survival but is dispensable for TORC1 function. 相似文献
909.
Panero J Trelles J Rodano V Montserrat JM Iglesias LE Lewkowicz ES Iribarren AM 《Biotechnology letters》2006,28(14):1077-1081
Enzymatic hydrolysis of acetylated nucleosides using microbial whole cells has been carried out for the first time. Unlike Candida antarctica B lipase-catalysed alcoholysis, none of the tested microorganisms displayed a common deacetylation profile. Depending on the substrate and the biocatalyst used, 5′-selective deprotection or mixtures of mono O-acetylated products were obtained. 相似文献
910.
We review the synthesis and photophysical properties of light harvesting phenylacetylene dendrimers with unsymmetrical branching.
We describe the steady state and time dependent experiments that are used to characterize energy transfer properties in the
conjugated dendrimers. Finally, we describe investigations of the unsymmetrical phenylacetylene dendrimers as potential materials
for applications in fluorescence-based sensors, and for non-linear optics. 相似文献