




版權(quán)說明:本文檔由用戶提供并上傳,收益歸屬內(nèi)容提供方,若內(nèi)容存在侵權(quán),請進(jìn)行舉報或認(rèn)領(lǐng)
文檔簡介
1、Molecular Medicine for Heart FailureIsozyme-specific Modulation of PKC lThe prevalence of heart failure in Australia is 6.3% .lThe heart failure prevalence is 10% in people aged over 65 years (this population will double over the next 50 years in Australia). Stages of heart failure from Goldman: Cec
2、il Medicine, 23rd ed Effusion from congestive heart failure from Mason: Murray & Nadels Textbook of Respiratory Medicine, 4th edMolecular Cell Biology underlying heart failure:PKC Activation and Heart FailureCirculation Research. 2019;101:195 J. Clin. Invest., 115:527,2005Activation of PKC and H
3、eart FailurePKC is activated by Gq/G11 -PLC -IP3-SR-released Ca+ and DAGSarcoplasmic Reticulum)Protein Phosphatase-1Phospholamban P ca+ uptake, increased Ca+ release & contractile force)Sarcoplasmic reticular calcium uptake proteinPKCa Ca+ cyclingReduced1-contraction strength2ralaxation3Cardiac
4、reservePKCa is activated by Ca+, stress agonists, pressure load, myocardial infarction, angiotensin, Transition in failing hearts fromadequate compensation To advanced failureProtein Phosphatase Inhibitor-1Calcium handling proteins:PLB, SERCA-2aDomain Structure of PKCATPN-LobeC-Lobe3-D structure of
5、PKADIFFICULTIES in structural determination of C-tailRole of the very C-termini of PKCsN-LobeC-LobeIntrinsic activity, protamine sulfate as substrate.DAG- activation Histone H1 as substrateS.S. Yeong, et al., J. Biol. Chem. 281:30768, 2019S.S. Yeong, et al., J. Biol. Chem. 281:30768, 2019The critica
6、l role of the very C-terminus of PKC-a in Augmenting Melatonin-stimulated Neurite Outgrowth in Neuronal CellsS.S. Yeong, et al., J. Biol. Chem. 281:30768, 2019S.S. Yeong, et al., J. Biol. Chem., 2019thrombintRNAC-terminus of PKC is exposed (accessible) from IP experimentsFluorescence Polarization-ba
7、sed screening. Homogenous assay system.Fluorescence Intensity-based screeningProf. Michael FamulokLaboratory of Chemical Biology University of Bonn lCommercial sources (free of royalty)l-NCI (/docs/misc/available_samples/dtp_indsamples.html)lStructural Diversity Set, version 1 (1,991
8、compounds) lStructural Diversity Set, version 2 (1,986 compounds) lMechanistic Diversity Set (879 compounds) lOpen Collection 1 (90,000 compounds) lOpen Collection 2 (10,000 compounds)l-ChemDiv (chemdiv)l-ChemBridge Corporation (chembridge/chembridge/)lPartnership with pharmaslPartnership with acade
9、mial MOLECULAR LIBRARIES SCREENING CENTERS NETWORK (Established in 2019)l 9 Centers Sources of Current or Off-patient medications-Prestwick Chemical Co. (1120 off-patient drugs)-Microsources: The Spectrum Collection (2000)-Sequoia (a large collection)-NIH Brain Bioactive Compound collectionEngineering nanoparticlesDrug loadingTargetingControlled Release (heat, magnetic field, pH), engineering the nanoparticle system such that the intracellular drug-release kinetics is greater than the drug-efflux kinetics Drugs administered at
溫馨提示
- 1. 本站所有資源如無特殊說明,都需要本地電腦安裝OFFICE2007和PDF閱讀器。圖紙軟件為CAD,CAXA,PROE,UG,SolidWorks等.壓縮文件請下載最新的WinRAR軟件解壓。
- 2. 本站的文檔不包含任何第三方提供的附件圖紙等,如果需要附件,請聯(lián)系上傳者。文件的所有權(quán)益歸上傳用戶所有。
- 3. 本站RAR壓縮包中若帶圖紙,網(wǎng)頁內(nèi)容里面會有圖紙預(yù)覽,若沒有圖紙預(yù)覽就沒有圖紙。
- 4. 未經(jīng)權(quán)益所有人同意不得將文件中的內(nèi)容挪作商業(yè)或盈利用途。
- 5. 人人文庫網(wǎng)僅提供信息存儲空間,僅對用戶上傳內(nèi)容的表現(xiàn)方式做保護(hù)處理,對用戶上傳分享的文檔內(nèi)容本身不做任何修改或編輯,并不能對任何下載內(nèi)容負(fù)責(zé)。
- 6. 下載文件中如有侵權(quán)或不適當(dāng)內(nèi)容,請與我們聯(lián)系,我們立即糾正。
- 7. 本站不保證下載資源的準(zhǔn)確性、安全性和完整性, 同時也不承擔(dān)用戶因使用這些下載資源對自己和他人造成任何形式的傷害或損失。
最新文檔
- 美容師考試提升方案及試題答案
- 2024年寵物營養(yǎng)師案例分析試題及答案
- 精神科癥狀學(xué)試題及答案
- 2024年非法改裝車評估難點試題及答案
- 汽車美容師行業(yè)資訊獲取與運用能力考核試題及答案
- 2024年美容師美學(xué)設(shè)計與市場趨勢試題及答案
- 醫(yī)療崗模擬面試題及答案
- 古代文學(xué)的價值觀念與文化傳承試題及答案
- 2024年統(tǒng)計學(xué)考試興趣激發(fā)試題及答案
- 食品檢測儀器使用的注意事項試題及答案
- 法理學(xué)-(第五版)完整版ppt全套教學(xué)教程課件(最新)
- 旅行管家實務(wù)全套ppt課件最全電子教案完整版教學(xué)教程整套全書課件ppt
- 三年級下冊數(shù)學(xué)課件-4.1 整體與部分 ▏滬教版 13張
- 稅務(wù)稽查管理-稅務(wù)稽查實施
- 變更稅務(wù)登記表doc-變更稅務(wù)登記表
- 基于單片機(jī)的智能路燈控制系統(tǒng)外文文獻(xiàn)
- 隧道保通安全專項方案
- 食材配送售后服務(wù)方案
- 天津人社局解除勞動合同證明書
- 風(fēng)力發(fā)電機(jī)軸電壓軸電流的研究
- 糖尿病護(hù)理新進(jìn)展
評論
0/150
提交評論