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SEVERO SALVADORI REMO GUERRINI PIERO ANDREA BOREA ROBERTO TOMATIS 《Chemical biology & drug design》1992,40(5):437-444
The synthesis of pseudotetrapeptides H-Tyr-D-Ala-Phe-NH-(CH2)2-NH2 (1a), H-Tyr-D-Ala-Phe-ψ(CH2-NH)-Gly-NH2 (2a), H-Tyr-D-Ala-ψ(CH2-NH)-Phe-Gly-NH2 (3a), and H-Tyr-ψ(CH2-NH)-D-Ala-Phe-Gly-NH2 (4a), representing the N-terminal tetrapeptide sequence of dermorphin, in which amide bonds are replaced by CH2-NH bond, is described. N-acetyl-Tyr and desamino-Tyr pseudopeptide analogs (1-4b), (1-3c) are also described. The analogs were assayed in binding studies based on displacement of μ and δ-receptor selective radiolabels from rat brain membrane and in a bioassay using guinea pig ileum (GPI). Pseudopeptides in which the C-terminal (1a) or D-Ala-Phe (3a) amide bond are substituted, exhibit higher μ-affinities and μ-receptor selectivity than the corresponding Phe-Gly or Tyr-D-Ala analogs (2a, 4a). Acetyl-and desamino-Tyr pseudopeptide analogs (1-4b) and (1-3c) did not exhibit μ and δ-opioid receptor affinity at nM concentration. The relevance of the single peptide replacement and of its association to acetylation or amino group elimination of Tyr, is discussed on the basis of a receptor model for μ and δ opioids. 相似文献
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The previously described cyclic delta opioid receptor-selective tetrapeptide H-Tyr-d -Cys-Phe-d -Pen-OH (JOM-13) was modified at residue 3 by incorporation of both natural and unnatural amino acids with varying steric, electronic, and lipophilic properties. Effects on mu and delta opioid receptor binding affinities were evaluated by testing the compounds for displacement of radiolabeled receptor-selective ligands in a guinea pig brain receptor binding assay. Results obtained with the bulky aromatic 1-Nal3 and 2-Nal3 substitutions suggest that the shape of the receptor subsite with which the side chain of the internal aromatic residue interacts differs for delta and mu receptors. This subsite of either receptor can accommodate the transverse steric bulk of the 1-Nal3 side chain but only the delta receptor can readily accept the more elongated 2-Nal3 side chain. Several analogs with pi-excessive heteroaromatic side chains in residue 3 were examined. In general, these analogs display diminished binding to mu and delta receptors, consistent with previous findings for analogs with residue 3 substitutions of modified electronic character. Several analogs with alkyl side chains in residue 3 were also examined. While delta receptor binding affinity is severely diminished with Val3, Ile3, and Leu3 substitutions, Cha3 substitution is very well tolerated, indicating that, contrary to the widely held belief, an aromatic side chain in this portion of the ligand is not required for delta receptor binding. Where possible, comparison of results in this delta-selective tetrapeptide series with those reported for analogous modification in the cyclic delta-selective pentapeptide [d -Pen2, d -Pen5]enkephalin (DPDPE) and linear pentapeptide enkephalins reveals similar trends. 相似文献
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用酸蚀法提高纯钛与光固化冠桥树脂粘结强度的研究 总被引:5,自引:1,他引:4
目的:研究用酸蚀法提高钛与光固化复合树脂剪切粘结强度的可行性,并观察表面粗糙度与剪切粘结强度之间的关系。方法:采用不同浓度的酸蚀剂对钛铸件表面进行酸蚀,并与artglass光固化复合树脂进行粘结,以单纯喷砂组为对照,比较剪切粘结强度的差异。对酸蚀后及剪切试验后的金属表面进行扫描电镜观察,并测定其表面粗糙度。结果:用酸蚀法可以显著提高钛与复合树脂的粘结强度,HF浓度为4%时粘结强度最高。表面粗糙度随酸蚀剂的浓度增高而下降。结论:纯钛铸件用酸蚀法处理后可以获得较高的粘结强度,HF酸浓度以4%为宜。表面粗糙度对粘结强度不起决定性作用。 相似文献
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Chemical catalysis, an effector mechanism utilized by fully assembled antibodies, can also be mediated by the isolated antibody subunits. Because trace amounts of free light chains (L chains) are present in IgG preparations, a detailed study was undertaken to identify the constituents responsible for the polyreactive proteolytic activity of IgG purified from human sera, determined as the extent of cleavage of the model peptide substrate Pro-Phe-Arg-methylcoumarinamide. Two proteolytic species with approximate mass of 50 kD and 150 kD were separated by repetitive gel filtration in a denaturing solvent (6 M guanidine hydrochloride). The activity of the renatured 50-kD fraction (in fluorescence units/microg protein) was more than 45-fold greater than of the 150-kD fraction. Both fractions lost the activity following immunoadsorption on immobilized anti-IgG antibody. Fab fragments prepared from the 150-kD IgG fraction retained the activity. Reducing and non-reducing SDS-electrophoresis suggested the 50-kD fraction isolated from the IgG preparations to be a mixture of heavy chain (H chain) monomers and disulphide bonded L chain dimers. Electrophoretically homogeneous monomers of 50-kD H chains and 25-kD L chains were prepared by gel filtration of reduced and alkylated IgG from seven human subjects. Each of the alkylated L chain preparations displayed the proteolytic activity. The activity in alkylated H chains was undetectable or only marginally greater than the background values. L chain dimers appear to be the major species responsible for the polyreactive proteolytic activity of serum IgG preparations, with a smaller contribution furnished by tetrameric IgG. 相似文献
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《Journal of labelled compounds & radiopharmaceuticals》2003,46(4):333-342
A new approach for 11C–C bond formation via a Sonogashira‐like cross‐coupling reaction of terminal alkynes with [11C]methyl iodide was exemplified by the synthesis of 17α‐(3′‐[11C]prop‐1‐yn‐1‐yl)‐3‐methoxy‐3,17β‐estradiol. The LC‐purified title compound was obtained in decay‐corrected radiochemical yields of 27–47% (n=8) based on [11C]methyl iodide within 21–27 min after EOB. In a typical synthesis starting from 9.6 GBq [11C]methyl iodide, 1.87 GBq of 17α‐(3′‐[11C]prop‐1‐yn‐1‐yl)‐3‐methoxy‐3,17β‐estradiol was synthesized in radiochemical purity >99%. The specific radioactivity ranged between 10 and 19 GBq/µmol, and the labeling position was verified by 13C‐NMR analysis of the corresponding 13C‐labeled compound. Copyright © 2003 John Wiley & Sons, Ltd. 相似文献
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The freeze–thaw resistant performance of a tunnel fireproof coating (TFC) has an important impact on bonding property and durability. The influence of redispersible emulsion powder, polypropylene fiber and air-entraining agent on TFCs was studied. Transverse fundamental frequency and ultrasonic sound velocity were used to evaluate the damage degree of TFC, and the mechanism was revealed by SEM and pore structure. The results show that the most beneficial effect on bond strength of TFC is redispersible emulsion powder, followed by air-entraining agent, and then polypropylene fiber. After freeze–thaw cycles, the cumulative pore volume of micropores in the TFC increases obviously, while the porosity of macropores does not change significantly. A prediction model was proposed, which can calculate the bond strength from the damage degree of TFC under freeze–thaw cycles. The achievement can promote the application of TFC in cold regions. 相似文献
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Nur Aziah Hanapi Ahmad Saifuddin Mohamad Arshad Jafri Malin Abdullah Tengku Sifzizul Tengku Muhammad Siti R. Yusof 《Journal of pharmaceutical sciences》2021,110(2):698-706
Neurotherapeutic potentials of Centella asiatica and its reputation to boost memory, prevent cognitive deficits and improve brain functions are widely acknowledged. The plant's bioactive compounds, i.e. asiaticoside, madecassoside and asiatic acid were reported to have central nervous system (CNS) actions, particularly in protecting the brain against neurodegenerative disorders. Hence, it is important for these compounds to cross the blood-brain barrier (BBB) to be clinically effective therapeutics. This study aimed to explore the capability of asiaticoside, madecassoside and asiatic acid to cross the BBB using in vitro BBB model from primary porcine brain endothelial cells (PBECs). Our findings showed that asiaticoside, madecassoside and asiatic acid are highly BBB permeable with apparent permeability (Papp) of 70.61 ± 6.60, 53.31 ± 12.55 and 50.94 ± 10.91 × 10?6 cm/s respectively. No evidence of cytotoxicity and tight junction disruption of the PBECs were observed in the presence of these compounds. Asiatic acid showed cytoprotective effect towards the PBECs against oxidative stress. This study reported for the first time that Centella asiatica compounds demonstrated high capability to cross the BBB, comparable to central nervous system drugs, and therefore warrant further development as therapeutics for the treatment of neurodegenerative diseases. 相似文献