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SESHA NATARAJAN STEPHEN M. FESTIN ANDERS HEDBERG EDDIE C.-K. LIU DAVID M. FLOYD JOHN T. HUNT 《Chemical biology & drug design》1992,40(6):567-574
We have developed an expeditious method for the incorporation of the biotinylaminocaproyl moiety on the ε-amino group of a lysine residue within a peptide chain in a site-specific manner. Using t-Boc chemistry for the solid phase synthesis approach and a base labile, acid stable protecting group (Fmoc-) for the ε-amino group of the target lysine, we prepared fully protected resin bound peptides which are site-specifically biotinylated. Following HF cleavage, the uniquely biotinylated peptides were obtained in a high degree of purity. Using this approach, a number of biotinylaminocaproyllysyl derivatives of a monocyclic Endothelin-1 analog were prepared. Synthesis of selected bicyclic analogs of high affinity monocycles led to the preparation of the bicyclic [Nle7]ET-1 analog containing ε-biotinylaminocaproyllysine at position-9. This peptide, with Kd= 0.08 nM, has 1000-fold higher affinity for the ETA receptor than the commercially available Nα-biotinylated Endothelin-1. The general utility of this biotinylation methodology was demonstrated by the synthesis of a site-specifically biotinylated PTH analog which contained several side chain functionalized amino acid residues in its sequence. The synthetic method reported here is convergent in that it allows the facile variation of the length of the spacer and also offers the potential to introduce in a site specific manner other groups such as affinity labels and fluorescent tags. 相似文献
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CHRISTIANE MENDRE VERONIQUE SARRADE BERNARD CALAS 《Chemical biology & drug design》1992,39(3):278-284
The continuous flow syntheses of endothelin 1, proendothelin 2. ATP binding site of the CDC2 kinase 3, and fragment 18-30 of an actin 4, have been performed by using a polyacrylamide gel resin Expansin? (about 0.6 mmol NH2/g) with the glycolamidic ester handle as labile anchorage. In addition, we report here a method of air oxidation which reduces the formation of side-products related to the formation of intermolecular disulfide bridges. 相似文献
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易丹丹 《杭州医学高等专科学校学报》2005,25(4):344-346
从非演绎方法入手,从分析与综合、归纳与概括、类比与联想三个方面联系歌唱的思维过程,论述非演绎思维方法在歌唱过程中的运用。思维的非演绎方法贯穿于歌唱的全过程,它们之间存在着紧密的联系。掌握思维的非演绎方法对于歌唱水平的提高有积极的促进作用。 相似文献
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Surojit Paul Peter Olausson Deepa V Venkitaramani Irina Ruchkina Timothy D Moran Natalie Tronson Evan Mills Shawn Hakim Michael W Salter Jane R Taylor Paul J Lombroso 《Neuropsychopharmacology》2007,61(9):1049-1061
BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders. 相似文献
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血管扩张药桂哌齐特的合成研究 总被引:6,自引:0,他引:6
目的:合成桂哌齐特。方法:以3,4,5-三甲氧基肉桂酸为起始原料,于室温下制成酰氯后与[(1-四氢吡咯羰基)甲基]哌嗪进行取代反应,再与顺丁烯二酸成盐即制得桂哌齐特。结果:经氯代、胺化和成盐3步反应合成桂哌齐特,总收率为36.1%。结论:该反应途径简单温和,适合工业化生产。 相似文献
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体外培养人增生性瘢痕成纤维细胞胶原合成及结缔组织生长因子的表达 总被引:9,自引:1,他引:8
目的 探讨结缔组织生长因子在人增生性瘢痕发病机制中的作用。方法 体外培养人正常皮肤和增生性瘢痕成纤维细胞 ,通过H3 脯氨酸掺入法检测细胞胶原合成 ,通过免疫细胞化学染色和逆转录聚合酶链反应检测细胞结缔组织生长因子蛋白质和mRNA的表达。结果 和正常皮肤成纤维细胞相比 ,增生性瘢痕成纤维细胞的胶原合成和结缔组织生长因子蛋白质及mRNA的表达均显著增高 (P <0 0 1)。结论 结缔组织生长因子可能在增生性瘢痕纤维化过程中发挥重要促进作用。 相似文献