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61.
Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol) 总被引:1,自引:0,他引:1
Ikuo Saiki Junya Yoneda Yu Igarashi Miho Aoki Naoto Kusunose Kei-ichi Ono Ichiro Azuma 《Cancer science》1993,84(5):558-565
Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)n (n = 1 to 11) and cyclo(RGDT)n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)11, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)11 exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)11 was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)11 significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)n, cyclo(RGDT)n and PEG-(RGDT)11 inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”). 相似文献
62.
Gijs A. Kleter Jan J. M. Damen Mark J. Buijs J. M. Ten Cate 《European journal of oral sciences》1997,105(3):278-284
The Maillard reaction between carbohydrate and protein has been proposed as a cause of the browning of carious lesions. The aim of the present investigation was to determine the occurrence of this reaction in bovine dentin collagen in vitro and to establish the effect of the reaction on the proteolytic degradation of bovine dentin collagen in vitro. Slices of demineralized bovine dentin were incubated with 0.2 M glucose or buffer for 10 weeks at 37°C. The formation of initial (furosine) and advanced (pentosidine) products of the Maillard reaction in dentin exposed to glucose was confirmed by HPLC. After reduction with NaBH4 to prevent intermediate Maillard products from further reaction, slices were either degraded with collagenase for fluorescence measurement or incubated with trypsin or pepsin to assess enzymatic degradation. Fluorescence characteristic for the Maillard reaction increased in glucose-exposed slices. Degradation of collagen by pepsin, but not by trypsin, was greatly depressed following glucose pretreatment. This may indicate an altered sensitivity to proteolytic degradation; the Maillard reaction thus has a potential role in caries arrestment. 相似文献
63.
Yu. A. Romashkova A. V. Danilkovich A. N. Valuiskikh V. V. Pershina K. B. Freze G. T. Sukhikh 《Bulletin of experimental biology and medicine》1997,123(4):388-390
Synthetic fragment of human interferon-2α (124th–138th amino acid residue, laboratory code 2438) inhibits the growth of B
lymphocytes (Daudi cell line) in a dose-dependent manner. Radiolabeled peptide 2438 binds to specific receptors on the cell
surface and competes with interferon-2α for the common binding sites.
Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 4, pp. 446–448, April, 1997 相似文献
64.
Attenuation of myocardial injury due to oxygen free radicals(OFR) by pretreatment with OFR or calcitonin gene-related peptide 总被引:3,自引:0,他引:3
目的:研究氧自由基(OFR)及降钙素基因相关肽(CGRP)预处置对OFR所致离体大鼠心脏损伤的拮抗作用.方法:Langendorf法灌流心脏,电解KH液产生OFR.结果:CGRP或OFR预处置减轻OFR所致心脏收缩功能下降,冠脉流量减少和肌酸激酶(CK)释放增加.蛋白激酶C(PKC)抑制剂H7可取消OFR预处置的心脏保护作用(对照组,OFR损伤组,OFR预处置组,H7加OFR预处置组及H7组的CK释放量分别是110±7,215±23,169±14,240±30,113±19U·L-1).结论:OFR或CGRP预处置对OFR所致心肌损伤具有拮抗作用,该作用与PKC激活有关. 相似文献
65.
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
66.
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
67.
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
68.
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
69.
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
70.
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