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101.
NOEL S. STURM ANN MARIE HUTZLER CLINTON S. DAVID BASSEM Y. AZIZEH DEV TRIVEDI VICTOR J. HRUBY 《Chemical biology & drug design》1997,49(4):293-299
We have designed and synthesized eight compounds 2-9 which incorporate neutral, hydrophobic amino acid residues in positions 9, 11 and 16 of the glucagon molecule: (2) [desHis1,Va19,11e11,16] glucagon amide, (3) [desHis1,Val9,11,16]glucagon amide, (4) [desHis1,Va19,Leu11,16]glucagon amide, (5) [desHis1,Nle9,11e11,16]glucagon amide, (6) [desHis1,Nle9,Val11,16]glucagon amide, (7) [desHis1,Nle9,Leu11,16]glucagon amide, (8) [desHis1,Val9,Leu11,16,Lys17,18,Glu21]glucagon amide and (9) [desHis1,Nle9,Leu11,16,Lys17,18,Glu21]glucagon amide. The effect of neutral, hydrophobic residues at positions 9, 11 and 16 led to good binding to the glucagon receptor. Compared to glucagon (IC50= 1.5 nM), analogues 2-9 were found to have IC50 values of 6.0, 6.0, 11.0, 9.0, 2.5, 2.8, 6.5 and 7.0 nM, respectively. When these compounds were tested for their ability to block adenylate cyclase (AC) activity, they were found to be antagonists having no stimulation of adenyl cyclase, with PA2, values of 6.15, 6.20, 6.30, 7.25, 6.10, 7.30, 6.25 and 7.25, respectively. © Munksgaard 1997. 相似文献
102.
The most commonly used photoaffinity labeling probes are compared, which are aryl azides, aryl diazirines, α-diazocarbonyls and benzophenone-derivatives. The compounds were used under identical conditions and crosslinking efficiency, influence of water, irradiation requirements, and by-products were investigated. Using the pentapeptide thymopentin (TP5) as a model system, we synthesized four analogues by solid-phase peptide synthesis and partially N-terminal modification to obtain [p-(3-trifluoromethyl)diazirinophenylalanine5] TP5, [p-benzoylphenylalanine5] TP5, 4-azidobenzoyl-TP5 and 2-diazo-3, 3, 3-trifluoropropionyl-TP5. The peptides were characterized by HPLC and ion-spray mass spectroscopy. Irradiation of the peptides with two different ultraviolet sources was carried out in water, n-propanol and water/n-propanol to imitate both hydrophobic and hydrophilic peptide/protein-interactions as well as the influence of the aqueous environment. Analysis of the products with HPLC, ion-spray MS, HPLC-MS and HPLC-CID-MS revealed that (Tmd)Phe is a highly potent carbene-precursor, which can be transformed easily into uniform crosslinking products by smooth photolysis. However, the electrophilic nature of the intermediate causes a high tendency to react with water molecules. The 4-azidobenzoyl group showed comparable crosslinking efficiency, but the probability to create non-uniform irradiation products (e.g. through rearrangement) is higher, whereas the reaction with water is less dominant. In contrast, Bpa was found to have an extremely low affinity to react with water, whereas prolonged UV irradiation is needed to get complete rearrangement into a variety of products. As the absorption band of α-diazocarbonyls at around 350 nm possesses a low extinction coefficient, 2-diazo-3, 3, 3-trifluoropropionyl-TP5 could not be activated at all with the optimized irradiation conditions that we have chosen for our comparative studies. © Munksgaard 1997. 相似文献
103.
根据由精氨酸-甘氨酸-天冬氨酸组成的肽能抑制血小板聚集的机制,设计并合成了[5-(4-甲脒-苄基)-2,4-二氧代-咪唑烷-3-基]-乙酰基-L-天冬氨酰-L-缬氨酸(9)。生物试验结果表明:(9)抑制血小板聚集作用最强,其活性以IC_(50)值相比,强于类似物。 相似文献
104.
P. MORSING A. STENBERG D. CASELLAS A. MIMRAN C. MÜLLER-SUUR C. THORUP L. HOLM A. E. G. PERSSON 《Acta physiologica (Oxford, England)》1992,146(3):393-398
Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure. The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop-flow pressure (Psf) was increased from 18.5 to 25.7 nl min-1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism. In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP. 相似文献
105.
蝎毒多肽对大鼠纤溶系统的作用 总被引:1,自引:0,他引:1
从蝎毒中获取具有多种药理活性的肽类混合物(简称SVP),用下肢血管灌流和整体给药的动物模型,观察对血管灌流液内纤溶酶原激活物(PA)活性、血浆优球蛋白纤溶活性(EFA)、纤溶酶(PL)活性的影响。结果:1~20μg/ml灌流3min和0.8,1.6mg·kg-1ipSVP1h血浆中PA活性与对照组相比明显升高(P<0.05或P<0.01),这可能与血管内皮细胞释放PA活性增加有关。 相似文献
106.
Background : The results of management of seminoma of the testis at the Department of Radiation Oncology St Vincent's Hospital, Sydney were evaluated retrospectively to: (i) establish that outcomes were in keeping with published results from centres in Australia and overseas; (ii) assess the impact of chemotherapy on management; and (iii) to determine ‘best practice’ management protocols based on our results and a review of the relevant literature. Methods : (i) Assessment of treatment results for stage I and II seminoma of the testis treated by post-orchidectomy radiotherapy and/or chemotherapy at St Vincent's Hospital between 1979 and 1993; (ii) literature review of published data from Australian and overseas centres on the management of seminoma of the testis, and in particular the use of surveillance or chemotherapy either alone, at time of relapse or combined with radiotherapy; and (iii) development of recommendations for use as management protocols in our department. Results : Our data and a review of the literature suggest that post-orchidectomy radiotherapy with chemotherapy for relapse in stage I and IIA disease results in long-term cure rates approaching 100%. Treatment with chemotherapy either routinely or selectively or using a surveillance policy is unlikely to show any improvement in outcome and may be less cost-effective and/or produce increased morbidity and the risk of secondary leukaemia. For stage IIB disease (5–10 cm) the use of initial combination chemotherapy with or without subsequent radiotherapy did not appear to give better outcomes than initial radical radiotherapy alone, reserving chemotherapy or further radiotherapy for relapse. For bulkier stage IIB disease (> 10cm). the use of initial chemotherapy plus consolidation radiotherapy appeared to be an appropriate treatment. Conclusions : Management protocols for seminoma of the testis at St Vincent's Hospital, Sydney Department of Radiation Oncology currently are (i) stage I, IA and IIB (5–10 cm): post-orchidectomy radiotherapy alone with chemotherapy or further radiotherapy for relapse; and (ii) stage IIB (> 10 cm) disease: initial chemotherapy post-orchidectomy followed by radiotherapy to sites of initial disease involvement. 相似文献
107.
108.
腰椎间盘突出症患者手术前后血浆内皮素及降钙素基因相关肽的变化 总被引:4,自引:0,他引:4
目的 探讨血浆内皮素 (ET)及降钙素基因相关肽 (CGRP)在腰椎间盘突出症(PLID)患者手术前后的变化及其意义。方法 采用放射免疫法检测 40例正常人及 40例患者手术前后的血浆CGRP及ET值。结果 40例PLID患者术前血浆ET值明显高于正常对照组 ,术后ET值明显低于术前 (P <0 .0 1) ,但患者术后血浆ET值与正常对照组差异无显著性 (P >0 .0 5 )。40例PLID患者术前血浆CGRP值与正常对照组比较差异无显著性 (P >0 .0 5 ) ,40例PLID患者术后疼痛明显改善 ,且其血浆CGRP值明显高于术前及正常对照组 (P <0 .0 1)。正常对照组ET与CGRP无明显相关 ,病组术前ET与CGRP呈正相关 ,而术后两者无明显相关。结论 ET与CGRP共同参与了PLID的发病过程 ,为探讨PLID保守治疗方法提供了依据。 相似文献
109.
110.
KLEOMENIS BARLOS DIMITRIOS GATOS OLGA HATZI NICOLE KOCH SOFIA KOUTSOGIANNI 《Chemical biology & drug design》1996,47(3):148-153
S-4-methoxytrityl cysteine was synthesized and converted into the corresponding Fmoc-Cys(Mmt)-OH by its reaction with Fmoc-OSu. As compared to the corresponding Fmoc-Cys(Trt)-OH, the S-Mmt-function was found to be considerably more acid labile. Quantitative S-Mmt-removal occurs selectively in the presence of groups of the tert butyl type and S-Trt by treatment with 0.5–1.0% TFA. The new derivative was successfully utilized in the SPPS of Tyr1-somatostatin on 2-chlorotrityl resin. In this synthesis groups of the Trt-type were exclusively used for amino acid side-chain protection. Quantitative cleavage from the resin and complete deprotection was performed by treatment with 3% TFA in DCM–TES (95:5) for 30 min at RT. We observed no reduction of tryptophan under these conditions. © Munksgaard 1996. 相似文献