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941.
Massimiliano Porcelli Mariano Casu Adolfo Lai Giuseppe Saba Massimo Pinori Silvana Cappelletti Paolo Mascagni 《Biopolymers》1999,50(2):211-219
Under the hypotheses of a structurally related binding site for antagonists of G‐protein coupled receptors and the ability of cyclic pentapeptides of chiral sequence D 1L 2D 3D 4L 5 to form rigid structures with which probe the pharmacophoric specificity of these receptors, inhibitors of substance P were designed based on available structure–activity relationships. ITF 1565, cyclo[D ‐Trp1‐Pro2‐D ‐Lys3‐D ‐Trp4‐Phe5], antagonized substance P activity mediated by type 1 neurokinin receptor (NK1) whereas it acted weakly against NK2 and did not inhibit endothelin at all. The preferential conformation of the peptide was obtained from nmr spectroscopy and computer calculations, and shown to contain the same βII‐turn and γ′‐turn found in other cyclic pentapeptides with the same chiral sequence. The structure of the peptide was compared with that of the β‐D ‐glucose molecule that has been proposed as a semirigid scaffold for antagonists of G‐protein coupled receptors. The γ′‐turn of the cyclic peptide superimposed well with β‐D ‐glucose in the chair conformation. Furthermore, when the side chains were considered, the aromatic groups of the two molecules were found to generally overlap. These results support the view of G‐protein coupled receptors as possessing structurally similar binding sites for antagonists and suggest that cyclic pentapeptides of chiral sequence D 1L 2D 3D 4L 5 may be useful as semirigid scaffolds for the design of antagonists of this family of receptors. © 1999 John Wiley & Sons, Inc. Biopoly 50: 211–219, 1999 相似文献
942.
Jingqiang Zheng Chaohong Guan Huangxu Li Danjun Wang Yanqing Lai Simin Li Jie Li Zhian Zhang 《Liver Transplantation》2024,14(15):2303584
The primary bottleneck hindering the application of hard carbon in sodium-ion batteries (SIBs) anodes lies in its inadequate initial Coulombic efficiency (ICE). Unclear causes of capacity loss at the microscopic level restrict the improvement of hard carbon anodes. Here, two pivotal stages that influence the structure and composition of hard carbon, namely synthesis, and storage are evaluated; subsequently identifying crucial determinants contributing to irreversible capacity loss. The results suggest that undergrown carbon layers allowing the intrusion of solvent molecules into the interior of the hard carbon is a key factor during the synthesis stage, while the gradual formation of oxygen-containing functional groups on the surface of the hard carbon is another factor leading to irreversible loss of capacity during storage stage. This research microscopically clarifies the irreversible capacity loss mechanism on hard carbon and provides guidelines for designing and applying high ICE hard carbon for SIBs. 相似文献
943.
Susan Barrera Joyce Lai Claudio Fiocchi James K. Roche 《Journal of cellular physiology》1996,166(1):130-137
Regulation of immune cell activation in lymphocyte-bearing human tissues is a pivotal host function, and metabolites of arachidonic acid (prostaglandin E2 in particular) have been reported to serve this function at non-mucosal sites. However, it is unknown whether prostaglandin E2 is immunoregulatory for the large lymphocyte population in the lamina propria of intestine; whether low (nM) concentrations of prostaglandin E2 modulate immune responses occurring there; and whether adjacent inflammation per se abrogates prostaglandin E2's regulatory effects. To address these issues, intestine-derived lymphocytes and T hybridoma cells were assessed, T cell activation was monitored by release of independently quantitated lymphokines, and dose-response studies were performed over an 8-log prostaglandin E2concentration range. IL-3 release by normal intestinal lamina propria mononuclear cells was reduced (up to 78%) in a dose-dependent manner by prostaglandin E2, when present in as low a concentration as 10−10M. PGE2 also inhibited(by ≥ 60%) mucosal T lymphocytes' ability to destabilize the barrier function of human epithelial monolayers. Further, with an intestine-derived T lymphocyte hybridoma cell line, a prostaglandin E2 dose-dependent reduction in IL-3 and IL-2 (90 and 95%, respectively) was found; this was true for both mitogen- and antigen-driven T cell lymphokine release. Concomitant [3H] thymidine uptake studies suggested this was not due to a prostaglandin E2-induced reduction in T cell proliferation or viability. In contrast, cells from chronically inflamed intestinal mucosa were substantially less sensitive to prostaglandin E2, e.g., high concentrations (10−6 M) of prostaglandin E2 inhibited IL-3 release by only 41%. We conclude that prostaglandin E2 in nM concentrations is an important modulator of cytokine release from T lymphocytes derived from the gastrointestinal tract, and it may play a central role in regulation of lamina propria immunocyte populations residing there. © 1996 Wiley-Liss, Inc. 相似文献
944.
James R. Corte Wu Yang Tianan Fang Yufeng Wang Honey Osuna Amy Lai William R. Ewing Karen A. Rossi Joseph E. Myers Steven Sheriff Zhen Lou Joanna J. Zheng Timothy W. Harper Jeffrey M. Bozarth Yiming Wu Joseph M. Luettgen Dietmar A. Seiffert Mimi L. Quan Patrick Y.S. Lam 《Bioorganic & medicinal chemistry letters》2017,27(16):3833-3839
Optimization of macrocyclic inhibitors of FXIa is described which focused on modifications to both the macrocyclic linker and the P1 group. Increases in potency were discovered through interactions with a key hydrophobic region near the S1 prime pocket by substitution of the macrocyclic linker with small alkyl groups. Both the position of substitution and the absolute stereochemistry of the alkyl groups on the macrocyclic linker which led to improved potency varied depending on the ring size of the macrocycle. Replacement of the chlorophenyltetrazole cinnamide P1 in these optimized macrocycles reduced the polar surface area and improved the oral bioavailability for the series, albeit at the cost of a decrease in potency. 相似文献
945.
946.
947.
Chen Liang Liu Feng Jia Fen Hu Ya-jun Lai Cui Li Xi Luo Pei Xiao Run-lin Li Yong Wu Jin-shui 《Applied microbiology and biotechnology》2017,101(3):1301-1311
Applied Microbiology and Biotechnology - Anaerobic ammonium oxidation (anammox) was suggested to be involved in the nitrogen (N) removal process in constructed wetlands (CWs). Nevertheless, its... 相似文献
948.
KCNQ1 variants associate with hypertension in type 2 diabetes and affect smooth muscle contractility in vitro
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Kuo‐Chin Huang Te‐Mao Li Xiang Liu Jin‐Hua Chen Wen‐Kuei Chien Yi‐Tzone Shiao Hsinyi Tsang Ting‐Hsu Lin Chiu‐Chu Liao Shao‐Mei Huang Ju‐Pi Li Cheng‐Wen Lin Jung‐Chun Lin Chih‐Chien Lin Chih‐Ho Lai Chi‐Fung Cheng Wen‐Miin Liang Chien‐Hui Hung Ching‐Chu Chen Ying‐Ju Lin Fuu‐Jen Tsai 《Journal of cellular physiology》2017,232(12):3309-3316
949.
Stimulatory actions of a novel thiourea derivative on large‐conductance,calcium‐activated potassium channels
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950.
Ran is involved in response to external stimuli. In this study, six MsRan gene cDNA sequences were isolated from wild banana (Musa spp. AB group) from Sanming City, China. Sequence analysis reveals that MsRan3A, MsRan3A-1a, and MsRan3C contained Ran protein domains including a GTP hydrolysis domain, a RanGAP-binding domain, and an acidic tail, whereas two G boxes (G4 and G5) were absent in MsRan3A-6a. The physicochemical property of MsRan3A, MsRan3A-1a, MsRan3A-6a, and MsRan3C appeared to differ significantly. Real time quantitative PCR (qPCR) analysis indicates that MsRan3A-1, MsRan3A-5, MsRan3A-6, MsRan3A-6a, and MsRan3C-1 were expressed in roots, leaves, peduncles, bracts, flowers, peels, and pulp of the wild banana. MsRan3A-1a was expressed at extremely low levels in these tissues and was undetectable by qPCR. The MsRan genes were found to be involved in responses to a low temperature stress but with different response patterns. Furthermore, salicylic acid significantly enhanced MsRan gene expressions suggesting the involvement of these genes in salicylic acid signal transduction. 相似文献