
AGScientific,Inc.成立于1997年,专注于创新生化制剂以及用于诊断测试开发的定制原材料,以推进临床前研究药物开发。产品涉及抗生素,生物洗涤剂,缓冲液,诊断,酶,医疗设备试剂,蛋白酶K,还原剂,RNaseA等。
CHAPS是一种两性离子洗涤剂,广泛应用于蛋白质纯化过程。作为这类洗涤剂的一部分,CHAPS含有一个正电荷和一个负电荷,但没有一个净的总电荷。CHAPS的生物膜亲和力相对较低,但在特定的浓度范围内可以有效地诱导溶血和蛋白溶解。CHAPS被归类为一种临界胶束浓度为6-10mM的非变性表面活性剂。
CHAPS的应用:在实验室中,CHAPS和其他两性离子洗涤剂可用于在分离蛋白之前诱导细胞裂解。它也可以用作二维凝胶电泳过程中的缓冲液,在某些情况下,它比SDS等阴离子洗涤剂更受欢迎。在蛋白质分析之前,可以通过透析从溶液中去除CHAPS。另一种技术利用专门的树脂和旋转柱也可以用来有效地去除皲裂用于监测化学反应或蛋白质结合的紫外/可见光谱学•用于离子交换色谱和等电色谱•用于细胞的膜渗透•以酶特性作为变性缓冲液的成分
嘌呤霉素盐酸盐是从阿氏链霉菌中分离得到的氨基糖苷类抗生素。嘌呤霉素是一种蛋白质合成抑制剂,它将自己整合到一个正在生长的多肽链中,导致其提前终止。嘌呤霉素的主要应用是作为基因选择抗生素,在CRISPR/Cas9基因编辑中发挥重要作用。这种以盐酸盐形式存在的嘌呤霉素试剂具有抗肿瘤、抗锥虫和抗菌的特性。重要的是要将嘌呤霉素盐酸盐储存在一个密闭的容器中,并置于通风干燥的地方。
盐酸贝斯他汀是氨基肽酶,氨基肽酶B,氨基肽酶M(CD13),和链霉菌来源的亮氨酸氨基肽酶(LAP3)的一种金属蛋白酶抑制剂。这些蛋白的抑制作用是由于肿瘤细胞的凋亡诱导。Bestatin在抗癌化疗、免疫调节、镇痛等方面表现出良好的疗效。
蛋白酶K(又称内肽酶K)是一种从真菌Tritirachiumalbumlimber培养滤液中分离出的胞外内肽酶。这种独特的真菌可以降解角蛋白(因此蛋白酶“K”),并可以利用其副产品作为碳和氮的唯一来源来生长。该酶在较宽的温度和pH范围内是稳定的,在55-65℃和pH8.0时是最佳活性。它在高盐浓度下也很稳定,在强洗涤剂如SDS的存在下也很活跃。其分子量为28.5kDa,对其多肽靶点的特异性较低。
AG蛋白酶K应用于下一代测序(NGS)和微阵列技术•核酸纯化,当从酵母、细菌、哺乳动物细胞和植物细胞裂解物中提取DNA和RNA时,通过灭活核酸酶来纯化核酸•提高PCR产物的克隆效率•使用加速器质谱法对DNA加合物水平进行定量的样品准备•核糖核酸酶保护试验中鸡尾酒酶的失活•添加到提取程序,以优化微阵列研究的原始乳腺肿瘤的RNA产量应用于蛋白质•检测具有独特抗蛋白降解能力的牛海绵状脑病蛋白。•组织消解作为另一种样品制备方法,用于液相色谱-串联质谱定量分析•特异性修饰细胞表面蛋白,分析膜结构进行蛋白定位•生成用于功能研究表征的蛋白片段
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不加磷酸化抑制剂也可以做磷酸化蛋白WB,但是有可能会影响具体的实验结果,大部分时候不加磷酸化抑制剂也能得到结果的。
需要注意蛋白的磷酸化是一个非常迅速的反应,所以取样品的过程要迅速,样品要新鲜。
所以做磷酸化蛋白WB,提取蛋白时不加磷酸酶抑制剂会有影响
酶抑制剂新药发现的途径:一是来源于天然化合物,包括动植物和各种微生物等,二是化学合成物。在目前上市的药物中,以受体为作用靶点的药物占52%,以酶为靶点的药物占22%,以离子通道为靶点的药物占6%,以核酸为靶点的药物占3%。因此,酶抑制剂的开发是新药来源的一个主要途径。以酶为靶点开发新药存在巨大潜力,今后很长一段时间仍然是发现新药的重要着手点。
Author:Shih IeM, Wang TL.
Resource:Cancer Res. 2007 Mar 1;67(5):1879-82.
Impact Factor:8.0(2005)
Abstract:The Notch signaling pathway represents a critical component in the molecular circuits that control cell fate during development. Aberrant activation of this pathway contributes to tumorigenesis. The role of Notch in human cancer has been highlighted recently by the presence of activating mutations and amplification of Notch genes in human cancer and by the demonstration that genes in the Notch signaling pathway could be potential therapeutic targets. It has become clear that one of the major therapeutic targets in the Notch pathway are the Notch receptors, in which gamma-secretase inhibitors prevent the generation of the oncogenic (intracellular) domain of Notch molecules and suppress the Notch activity. This review article summarizes the biological roles of Notch molecules in cancer development with special emphasis on the promise and challenges in applying gamma-secretase inhibitors as a new line of targeted therapeutic agents.
PMID: 17332312
A9 B12 C17 D36
正确答案C
一次氧化的产物不是乙酰COA么,那么产生的ATP为什么不是十个
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Exercisedampensaromataseinhibitor–relatedjointpain
http://www.internalmedicinenews.com/specialty-focus/oncology-hematology/single-article-page/exercise-dampens-aromatase-inhibitor-related-joint-pain/33383ff19a0cd42399a7cf8590708ebf.html
SANANTONIO–Adoptingastandardexerciseprogramresultedinaclinicallymeaningful30%reductioninaromataseinhibitor-associatedjointpaininbreastcancerpatientswhoparticipatedinayear-longrandomizedtrial.
TheexerciseprescriptionutilizedintheHOPE(HormonesandPhysicalExercise)trialwaswhat’srecommendedinnationalguidelinesbothforcancersurvivorsandhealthyadults:150minutesperweekofatleastmoderate-intensityaerobicactivity,suchasbriskwalking,alongwithtwostrength-trainingsessionsperweek,MelindaL.Irwin,Ph.D.,explainedattheSanAntonioBreastCancerSymposium.
TheHOPEstudiesenrolled121postmenopausalwomenwhohadstage1-3,hormonereceptor–positivebreastcancersandwerephysicallyinactiveandoverweightyetphysicallyabletoexercise.Atenrollment,theywereexperiencingmoderatearomataseinhibitor(AI)–associatedjointpain,definedasascoreof5-7onthe0-10BriefPainInventory(BPI),afterabout18monthsonthemedication.Roughlytwo-thirdsofparticipantshadnohistoryofjointpainpriortostartingAItherapy;therestreportedtheAIexacerbatedtheirpreexistingjointpain.Subjectswererandomizedtotheexerciseprogramortousualcare,whichincludedwritteninformationabouttheimportanceofexercise.
Theprimarystudyendpointwasthe12-monthchangeinBPIworstpainscore,whichdroppedbyanaverageof30%amongtheexercisegroup.Thistranslatedtoanimprovementinpainlevelfrommoderateatbaselinetomildatfollow-up.Inaddition,BPIscoresratingpainseverityandpaininterferenceimprovedbyabout20%.Incontrast,patientsintheusualcarecontrolgroupexperiencedaslightincreaseinBPIscoresinallthreedomainsovertime,addedDr.Irwin,co-leaderofthecancerpreventionandcontrolresearchprogramatYaleUniversityCancerCenter,NewHaven,Conn.
TheHOPEresultsreceivedanenthusiasticaudiencereception.Physicianswereparticularlyimpressedwiththe70%exerciseadherencerateoverthecourseofayear.Theyaskedhowtheycankeeptheirpreviouslysedentarypatients’commitmenttoregularexercisefromwaningafteraninitialburstofenthusiasm,assooftenhappens.
Dr.Irwinrepliedthatadherencetolifestylechangeisalwaysachallenge.Socialsupportisquitehelpful.TheexercisegroupinHOPEreceivedapaidgymmembershipandmetinsmallgroupswithapersonaltrainertwiceweekly.
"Thewomenreallybondedwitheachother.Andtherearenowagrowingnumberoffreeprogramsthroughoutthecountry,whichgivecancersurvivorsastartonanexerciseprogramwithafreegymmembershipforseveralmonths.Forexample,theLivestrongFoundationhaspartneredwiththeYMCAtoofferfreeexerciseprogramsforcancersurvivorsatlocalYs,"shesaid.
TheHOPEtrialwasfundedbytheNationalCancerInstitute.Dr.Irwinreportedhavingnofinancialconflictsofinterest.
Thisdegreeofimprovementinjointpainisgreaterthanreportedinstudiesofglucosamine,acupuncture,orvitaminDsupplementation,shenoted.
Theimprovementinpainscoresintheexercisegroupwasgreaterat12monthsthanat3or6,suggestingthatayear-longexerciseprogramisprobablynecessarytoseesustainedreductioninjointpain.
At12monthsoffollow-up,womenintheexercisegroupaveraged159minutesofphysicalactivityperweek,110minutesmorethancontrols.Compliancewiththesupervisedexerciseprogramwasnotablygood,withwomenattendinganaverageof70%ofthetwice-weeklysmall-groupstrength-trainingsessions.
InadditiontotheimprovementinAI-relatedarthralgias,theexercisegroupexperiencedancillarybenefits:amean6.5%improvementinpeakoxygenconsumption,orVO2max,comparedwithbaseline,alongwitha3%reductioninbodyweight.
HOPEwasthefirstrandomizedtrialtoexaminetheeffectsofexerciseonAIsideeffectsinbreastcancerpatients.TheimpetusforthestudywastherecognitionthatarthralgiasarethemostcommonreasonforpooradherencetoanddiscontinuationofAItherapy.Upto20%ofbreastcancerpatientsdiscontinuetheirAIwithinthefirstyear.Andbothearlydiscontinuationandpooradherencehavebeenshowntobepredictiveofincreasedmortalityrisk.

