肥大细胞脱颗粒肽的研究进展

肥大细胞脱颗粒肽是从蜂毒液中分离出的小分子肽，它具有较强的抗炎活性，但又能促使肥大细胞脱颗粒释放组胺。同时对电压依赖性钾通道具有阻断效应，具有神经毒素作用。本文综述近年来对肥大细胞脱颗粒肽的研究进展。     

生物活性肽药理活性的研究进展

随着人们生活水平的提高,伴随现代文明而来的各种富裕病如高血压、高血脂、肥胖病、癌症等越来越引起人们的关注,人们的消费观念已从单纯的吃饱吃好向防病治病方向转变.生物活性肽来源很广,目前已经成为世界范围内研究的热点.大量研究已表明,生物活性肽具有多种药理活性,如神经、激素和免疫调节、抗血栓、抗高血压、抗胆固醇、抗细菌病毒、抗癌作用等,是筛选药物的天然药物宝库.本文综述了生物活性肽的药理活性的研究进展.     

生物活性肽的研究进展

从生理活性肽和食品感官肽两方面综述了生物活性肽的研究动态，同时对一些肽作了结构与功能的描述。     

胸腺五肽及其衍生肽的杀菌活性研究

目的:研究胸腺五肽及其衍生肽的杀菌活性。方法:采用琼脂铺板计数法测定胸腺五肽[精氨酸(R)-赖氨酸(K)-天冬氨酸(D)-缬氨酸(V)-酪氨酸(Y),RKDVY]及其衍生肽1[RKN(天冬酰胺,N)VY]、衍生肽2(RKKVY)对革兰阴性(G-)菌(变形杆菌、大肠埃希菌)和革兰阳性(G+)菌(金黄色葡萄球菌、粪肠球菌)的杀菌活性,其中五肽剂量为15.625~1 000μg/ml,细菌数为102CFU。结果:3种五肽对G-菌均有杀菌活性,且RKKVY、RKNVY杀菌活性强于RKDVY(P<0.01),RKKVY与RKNVY间差异无统计学意义(P>0.05);对G+菌亦有杀菌活性,其杀菌活性由强到弱依次为RKKVY>RKNVY>RKDVY(P<0.01)。结论:胸腺五肽及其衍生肽对G-菌和G+菌均有杀菌活性,具有量效关系。     

海洋生物活性肽及其生物活性研究进展

概述存在于海绵、海鞘等海洋低等生物和海洋鱼贝类中的生物活性肽，以及这些活性肽的抗肿瘤、抗菌、抗高血压及抗氧化等生物活性的研究进展。     

卵清蛋白肽的制备及生物活性研究进展

鸡蛋作为人体补充蛋白质的主要来源之一,在市场中占有较大份额,但蛋类深加工产品的研发及市场拓展尚不十分充分。采用蛋白酶水解食物蛋白制备的小分子肽易吸收,并对人体健康发挥积极作用。近年来,卵清蛋白酶解制备的卵清肽被广泛研究,其生物功能得到逐步揭示,包括抗氧化、降压、抗菌、免疫调节、抗炎、降糖等。卵清肽的深入研究有利于充分利用禽蛋资源,提高其附加值,且卵清肽有望应用于食品、化妆品及医药用品等领域,具有较好的经济效益和社会效益。本文对卵清蛋白肽的制备工艺与生物活性进行概述,旨在为其进一步开发与应用提供有益参考。     

几种免疫活性肽的研究进展

生物体内存在一类具有活性的多肽 ,称为活性肽。它们在本内一般含量较低 ,结构多样 ,属体内的化学信息传递物质。活性肽通过内分泌、旁分泌、神经分泌等多种作用方式行使其功能 ,沟通各类细胞间的相互联系。本文仅就近年新发现及研究较多的几类免疫活性作一阐述。1　免疫活性肽概况免疫活性肽包括细胞因子 ,还有来源于植物和动物及致病微生物的免疫诱导肽。细胞因子是一类由免疫细胞 (淋巴细胞、单核 巨噬细胞等 )及相关细胞 (成纤维细胞、内皮细胞等 )产生的调节细胞功能的高活性多功能蛋白质多肽分子。此外 ,早在上世纪末 ,人们就注意到…     

新型非甾体抗炎药醋氯芬酸的研究进展

醋氯芬酸(Aceclofenac),化学名称2-[(2,6-二氯苯基)胺基苯基]乙酰氧基乙酸,是一种新型的强效非甾体抗炎剂,临床用于治疗类风湿性关节炎和术后疼痛〔1〕。它能降低炎痛部位前列腺素的生物合成,具有明显广泛的抗炎作用、强力镇痛和解热作用,其生物半衰期比双氯芬酸长,胃肠耐受性高。与同类药物比较,醋氯芬酸有治疗指数好,溃疡指数低等特点〔2〕。本品由西班牙Prodesfarana公司于1992年开发上市,之后陆续在瑞典、英国、比利时等国上市使用,1998年被收入欧洲药典和英国药典。目前,在我国醋氯芬酸被多家科研单位及企业开发研究,有多种制剂产品已…     

鸡源性活性肽的研究进展

随着我国鸡养殖和加工能力的提高,人们不仅追求鸡肉来源的营养成分,同时更需要提高其保健价值,其中鸡源性活性肽的生物活性及产业化应用备受人们关注。鸡源性活性肽不仅具有不同于蛋白质及氨基酸的消化吸收特性,还具有抗氧化、抗炎、免疫调节等诸多生物活性。此外,鸡肉加工副产物鸡骨、鸡皮、鸡血及鸡内脏等也是制备活性肽的主要原料,因而极大地减少了资源的浪费与环境污染。本文对鸡源性活性肽的制备、分离纯化、生物活性以及产业化应用等进行了概述,旨在为鸡源性活性肽的进一步开发利用提供有益的依据。     

昆虫抗菌肽抗炎活性及基于信号通路抗炎机制的研究进展

昆虫抗菌肽是昆虫为抵御外界病原微生物感染产生的免疫活性物质的总称,其优异的抗炎活性使其具有广阔的应用前景。综述了不同种类昆虫抗菌肽的抗炎活性及可能涉及的信号通路,介绍了昆虫抗菌肽临床研究现状,以期为昆虫抗菌肽的应用研究提供文献参考。     

Synthesis of new diselenide compounds as anti-inflammatory agents

Many diselenide compounds are used as antioxidants, enzyme inhibitors and cytokine inducers. Three new diselenide compounds, bis-(2-hydroxyphenyl) diselenide, bis-(3-hydroxyphenyl) diselenide and bis-(4-hydroxyphenyl) diselenide were designed and synthesized as anti-inflammatory agent. All of them were found to have strong in vitro activity in anti-inflammatory assays.     

Synthesis and biological screening of some novel 6-substituted 2-alkylpyridazin-3(2H)-ones as anti-inflammatory and analgesic agents

Some novel derivatives of 2-alkyl 6-substituted pyridazin-3(2H)-ones were synthesized by condensation of 3,6-dichloropyridazine with the sodium salt of benzyl cyanide, followed by hydrolysis and coupling with alkyl halides. The synthesized compounds were screened as cyclooxygenase (COX)-1/COX-2 inhibitors and as analgesic and anti-inflammatory agents. Among the synthesized compounds, 6-benzyl-2-methylpyridazin-3(2H)-one ( 4a ), 6-benzoyl-2-propylpyridazin-3(2H)-one ( 8b ), and 6-(hydroxy(phenyl)methyl)-2-methylpyridazin-3(2H)-one ( 9a ) displayed the highest COX-2 selectivity indices of 96, 99, and 98, respectively, and analgesic efficacies of 47%, 46%, and 45% protection, respectively. Also, compounds 4a , 8b , and 9a showed anti-inflammatory activities of 65%, 60%, and 62% inhibition of edema, respectively, at a dose of 10 mg/kg, which is higher than that of diclofenac (58% inhibition of edema).     

Synthesis of new (Nalpha-dipicolinoyl)-bis-L-valyl-L-phenylalanyl linear and macrocyclic bridged peptides as anti-inflammatory agents

In continuation to our search for new chiral macrocyclic peptide-based anti-inflammatories, the suggestion, synthesis, structure elucidation of some Nalpha-bis-dipicolinoyl amino acids, linear, tetra and cyclic (penta and octa)-bridged peptides 3-10, were realized herein. The newly synthesized compounds showed potent anti-inflammatory activity with low toxicity (LD50) comparable to indomethacin and diclofenac as reference anti-inflammatory drugs.     

Synthesis of certain uracil-6-yl or tetrazol-5-ylpyrazolin-5-one and pyrazole derivatives as potential anti-inflammatory agents

Certain pyrazolin-5-one and pyrazole derivatives bearing uracil-6-yl or tetrazol-5-yl moiety in position 1 have been synthesized. The anti-inflammatory activity of six representative compounds have been tested and the results are reported.     

Simultaneous multiple synthesis and selective conjugation of cyclized peptides derived from a surface loop of a meningococcal class 1 outer membrane protein

Starting from the α-(2,4-diniethoxybcnzyl) ester of N-(9-fluorenylniethoxycarbonyl)aspartic acid [Fmoc-Asp-ODmb], side-chain-protected resin-bound Fmoc-peptides containing an N^c-l-(4,4-dimethyl-2,6-dioxocyclohexylidenc)ethyl lysY1 [Lys(Dde)] residue were prepared. The C-terminal dimethoxybenzyl esters of aspartic acid were removed with 1% trifluoroacetic acid and 10% anisole in dichloromethane, followed by Fmoc-cleavage in the usual manner. The resin-bound peptides were then cyclized using 1-benzotriazolyloxy-tris-[N-pyrrolidino]phosphonium hexafluorophosphate (PyBOP) in the presence of N-methylmorpholine. The (dimethyldioxocyclohexylidene)ethyl groups of lysine were removed with 1% hydrazine hydrate in N,N-dimethylacetarnide, and the liberated side-chain amino functions were modified by reaction with pentafluorophenyl S-acetylinercaptoacetate (SAMA-OPfp). Finally, the peptides were side-chain deprotected, with exception of the Lys(SAMA) residue. and cleaved from the solid support with trifluoroacetic acid/anisole/ water, 95/2.5/2.5. Cyclic peptides comprising 7–14 amino acid residues were obtained employing this procedure. As a model conjugation. cyclo[Thr-Asn-Asn-Asn-Leu-Lys(SAMA)-Thr-Lys-Asp] was coupled with bromoacetamide. The same peptide was also coupled with a bromoacetylpeptide to give a well defined peptide1 peptide conjugate. All peptides were conjugated to bromoacetylated tetanus toxoid for immunization purposes.     

Design and synthesis of amphipathic antimicrobial peptides

A large proportion of antimicrobial peptides share a common structural feature that is critical to their antimicrobial activity, i.e. amphipathic α-helices. The amphipathy of a polypeptide chain can be quantitated through the value of the hydrophobic moment. Generally, antimicrobial peptides are characterized by high hydrophobic moment and low hydrophobicity values. Using these criteria we have identified two short segments that possess hydrophobic moment properties associated with known antimicrobial peptides. Using in vitro assays the segment derived from the protein perforin displays no antifungal or antibacterial activity and, while showing no α-helicity in buffer or liposomes, exhibits a modest degree of α-helical structure in the presence of the a-helical inducer, 2,2,2-trifluoroethanol. However, rational modifications result in a derivative which assumes an α-helical conformation in the presence of liposomes, exhibits potent antifungal activity against plant fungal pathogens, has significant antibacterial activity, effects leakage of a fluorescent dye from acidic liposomes and is devoid of hemolytic activity. Results are also presented for a segment derived from the human immunodeficiency virus envelope protein. We suggest that the identification of putative amphipathic structures in proteins may provide a useful starting strategy in the design and synthesis of antimicrobial peptides.     

非甾体抗炎药ML4000的合成及生物活性研究

目的:合成非甾体抗炎药ML4000并研究其生物活性。方法:ML4000以环氧合酶(COX)和5-脂氧合酶(5-LOX)双重抑制剂利克飞龙(licofelone,ML3000)为先导化合物,结构上链接了1个一氧化氮(NO)供体;通过灌胃给药,观察ML4000在动物体内的初步代谢、抗炎活性、胃肠道作用以及血清和胃黏膜NO水平。结果:ML4000经IR,MS,1H NMR,13C NMR以及元素分析等确证结构;大鼠灌胃ML4000(10 mg.kg-1)0.25 h后,即可测到ML4000代谢为ML3000;ML4000抗炎活性与ML3000相当;连续14 d灌胃(60mg.kg-1,qd),未见大鼠胃肠道出血;灌胃给药(60 mg.kg-1)1 h后大鼠血清和胃黏膜NO量显著增加。结论:合成的ML4000具有较强的抗炎作用,胃肠道耐受性好,并能够释放出NO。     

Synthesis and biological activity of Ub2 derived peptides as potential host‐directed antitubercular therapy

The correlation of mycobactericidal property of macrophages with its potential to deliver bacteria to hydrolytic lysosomes, augmented with ubiquitin‐derived peptides (Ub2), activates the process of autophagy. This leads to the formation of phagolysosomes supported by factor involving increased cationic charges which regulate the acidic pH causing elimination of Mycobacterium. To better understand this interaction of cationic‐rich ubiquitin‐derived peptides with mycobacteria and to identify putative mycobacterial intrinsic resistance mechanisms for phagolysosome formation, we have synthesized a new series of Ub2 peptides, wherein the Gly residues are replaced with azaGly with the aim to improve metabolic stability. In addition to that a new methodology is reported for the synthesis of heteroaryl tethered peptides using azaGly as a linker. We have demonstrated that positive puncta (directly proportional to the acidification of lysosome) in cytosol was significantly increased after 6 hours on the treatment of macrophage with Ub2 peptide derivatives ( 1 , 6 , 10, and 11 ) causing the higher intensity of lysosome observed through LysoTracker Red Dye. The circular dichroism spectral studies are carried out in water and water:TFE mixture and demonstrated that the Ub2 peptides have helix‐forming tendency in the presence of TFE. The recognizable intracellular killing of Mycobacterium tuberculosis by Ub2 peptides provides a new approach for host‐directed therapy.