English
聯系我們
網站地圖
郵箱
舊版回顧



我國科學家為活細胞蛋白質安裝“調控開關”

文章來源:光明日報 晉浩天   發布時間:2019-05-10  【字號:     】  

  北京大學化學與分子工程學院、合成與功能生物分子中心陳鵬課題組與王初課題組,8日在《自然》雜志在線發表題為《基于鄰近脫籠技術的活體內蛋白質瞬時激活》的研究論文,報道了兩個課題組合作發展的一種在活體環境下瞬時激活蛋白質的化學生物學新技術。

  在活細胞等生理環境下開展蛋白質功能的原位研究具有重要的科學意義。陳鵬課題組長期致力于發展蛋白質的原位激活技術,希望為活細胞內的每一個蛋白質安裝“調控開關”。最近,他們與王初課題組展開合作,提出并發展了一種蛋白質“鄰近脫籠”策略,將可遺傳編碼的非天然氨基酸脫籠技術與計算機輔助設計篩選技術相結合,在一系列不同種類的蛋白質上實現了高時間分辨的原位激活,為在活細胞及活體動物內研究蛋白質的動態調控機制提供了一種普適性技術。利用這一被命名為CAGE-prox的新方法,他們建立并驗證了“激酶正交激活和信號轉導調控”“時間分辨的蛋白質組學分析”“基于毒素蛋白的抗腫瘤蛋白前藥”等一系列原創應用,展示了這一化學生物學新技術在開展蛋白質動態功能研究與調控中的優勢和特色。

  陳鵬課題組先前提出的“化學脫籠”策略,可通過對蛋白質關鍵殘基的化學保護和脫保護反應,實現對其活性的“關-開”調控。利用這一技術,他們先后在賴氨酸、酪氨酸等天然氨基酸側鏈上實現了生物正交斷鍵反應和化學脫籠,開展了激酶等蛋白質家族的特異激活和機制研究。由于細胞內蛋白質的種類繁多、活性調控機制各異,目前該方法仍受可供脫籠的氨基酸種類限制,無法適用于所有蛋白質。

  為了解決這一問題,陳鵬課題組與王初課題組合作提出了“鄰近脫籠”的新策略,通過向蛋白質活性中心附近引入一種帶有光保護基團的非天然酪氨酸,可同樣實現對其活性的遠程干擾和抑制;隨后通過“光脫籠”反應將保護基團移除,使其活性重新恢復。由于在蛋白質活性口袋附近插入非天然酪氨酸后能夠通過影響蛋白穩定性、底物結合等多種因素調控蛋白質活性,該策略將原有的“活性位點脫籠”轉變為“活性口袋脫籠”,極大地擴展了該方法的適用范圍。

  中科院院士、北京大學醫學部教授張禮和表示,陳鵬課題組此前率先利用基于生物正交斷鍵反應的化學脫籠策略,結合遺傳密碼子拓展技術,實現了在蛋白質催化位點的生物正交脫籠,進而原位激活其功能。在最新的工作中,陳鵬課題組與北大王初課題組合作,進一步提出并發展了“鄰近脫籠”的新策略,利用計算機輔助設計與篩選,將蛋白質脫籠技術的適用范圍從催化位點拓展至整個活性口袋,獲得了具有廣泛適用性的蛋白質激活新方法。該工作是化學生物學領域的一項重要進展,為在活細胞及活體動物內開展蛋白質動態功能研究提供了關鍵技術,也為生物正交反應開拓了新的前沿方向。

  據悉,北京大學前沿交叉學科研究院博士畢業生王杰、化學與分子工程學院博士后劉源、研究生劉衍軍為該論文共同第一作者,陳鵬教授和王初研究員為本文的共同通訊作者。該項工作得到了國家自然科學基金委、科技部、教育部、北京分子科學國家研究中心和北大—清華生命科學聯合中心的資助。




(責任編輯:侯茜)

附件:

專題推薦

相關新聞


© 1996 - 中國科學院 版權所有 京ICP備05002857號  京公網安備110402500047號  聯系我們

地址:北京市三里河路52號 郵編:100864

PK彩票www.www.23040.com www.020108.com | www.137880.com | www.653089.com | www.972393.com | 950862.com | www.rd66.com | 169523.com | www.226845.com | www.ev94.com | 370252.com | www.8029.cm | www.43336.com | www.91736.cc | www.04895.com | www.5925.in | www.30596.com | www.155410.com | www.483111.com | www.559061.com | www.708387.com | www.974143.com | www.967541.com | 6678彩票www.2688cai.com | www.70wf.com | www.099806.com | 996007.com | www.207.shop | 088241.com | www.63pq.com | www.800615.com | www.321707.com | www.742678.com | 九州彩票www.www.6769a1.com | www.183721.com | 114892.com | www.035898.com | www.369904.com | www.no96.com | www.74gs.com | www.57585.cc | www.154598.com | www.633355.com | www.620611.com | 874145.com | 038323.com | www.972869.com | www.870458.com | www.738587.com | www.968033.com | 4057.net | www.825876.com | 011292.com | www.507678.com | 470059.com | 017838.com | www.571748.com | 850094.com | www.626229.com | www.365675.com | www.058217.com | www.253863.com | www.954554.com | www.z49.club | www.333041.com | www.446360.com | www.474479.com | www.510159.com | www.616961.com | www.953082.com | www.4ds.cc | www.41uo.com | www.035233.com | 941341.com | www.ia11.com | www.15si.com | www.8265.me | www.74566.cc | www.877355.com | www.gy47.com | 365129.cc | www.992.cc | www.713680.com | 984724.com | 579712.com | www.27pj.cc | www.980174.com | www.975306.com | www.935369.com | www.770082.com | www.q94.com | www.112246.com | www.hh37.com | www.8193.pw | www.6030.cm | 287329.com | www.110460.com | www.jb56.com | www.913193.com | www.52213.cc | www.042605.com | www.161803.com | 818258.com | www.061666.cc | www.242113.cc | www.m83.space | www.331396.com | www.881364.com | 067467.com | 069564.com | www.32353.cc | www.817577.com | 208258.cc | www.9860.org | www.292719.com | www.9834.org | 268976.com | www.981977.com | www.720809.com | www.102533.com | www.15331.com | www.4326.vip | www.4669.xyz | www.568555.cc | www.431112.com | www.526226.com | www.362086.com | www.96151.cc | 大赢家彩票平台www.132031.com | www.996282.com | www.375572.com | www.036561.com | www.zy43.com | www.988.cm | www.206338.com | 012251.com | www.910669.com | www.611111.cc | 421990.com | 948841.com | www.44074.com | www.307298.com | www.341198.com | www.815589.com | 奔驰彩票www.750966.com | www.1814.org | www.0838.org | www.355051.com | 773051.com | sn06.com | dc54.com | www.ns86.com | www.507236.com | www.88467.cc | 80858.com | www.877227.com | www.119163.com | www.528372.com | 大赢家彩票平台www.221075.com | www.00702.com | www.22815.cc | www.684111.com | www.054976.cc | www.420743.com | www.501970.com | www.68zd.com | www.654105.com | www.808003.com | www.880338.com | 380771.com | www.835520.com | www.084433.com | www.06308.com | www.of88.com | 019123.com | www.335078.com | www.493766.com | www.801994.com | www.77226.cc | www.428385.com | www.rh79.com | www.70oc.com | www.6216.cm | www.175598.com | www.716822.com | www.686070.com | www.739406.com | www.723298.com | www.1680.cn | www.967832.com | 181777.com | www.013928.com | www.x35.cn | www.373630.com | www.080630.com | www.216933.com | www.403511.com | www.63308.com | www.539686.com | www.768236.com | 126247.com | www.93716.cc | www.5583.vip | 9022.biz | 240442.com | www.454000.com | www.70701.cc | www.077289.com | www.tg63.com | www.v71.com | www.059603.com | www.256851.com | www.677163.com | www.cp057.com | www.133074.com | www.ft48.com | 356302.com | www.344559.com | 367333.com | 781423.com | www.44tn.com | www.229126.com | www.777490.com | 345336.cc | www.dl92.com | www.110479.com | www.280976.com | 029651.com | 303269.com | 022932.com | www.619500.com | www.002375.com | www.8279.xyz | 380062.com | 014144.com | www.200112.com | www.246960.com | www.751521.com | 033983.com | 528160.com | www.140446.com | www.466466.com | www.437859.com | 539704.com | 500彩票www.946277.com | www.176353.com | www.523231.com | 248147.com | 365939.cc | www.5347.cm | www.008785.com | www.088001.com | www.484679.com | www.639418.com | www.002969.com | www.123949.com | www.585569.com | www.t30.me | 500彩票网www.903029.com | www.3668.com | www.n91.club | 创世纪彩票www.36787j.com | www.95762.com | www.334218.com | www.988955.com | www.679264.com | 490525.com | www.081578.com | www.765290.com | www.985483.com | www.875381.com | www.cai689.com | www.cu1.com | www.04he.com | www.204072.com | www.538603.com | www.194593.com | www.2567.in | 9998.cc | www.884432.com | www.176052.com | www.573422.com | www.022843.com | www.239777.com | www.835791.com | www.789635.com | www.9813.biz | www.731125.com | www.975304.com | www.ow83.com | www.65oh.com | www.003913.com | www.95967.com | www.903082.com | 679094.com | www.65bu.com | www.59271.cc | www.288515.com | www.257117.com | www.269010.com | www.639124.com | www.646838.com | www.8529.in | www.46399.com | www.312873.com | www.521018.com | www.778448.com | www.oq86.com | 510738.com | www.843422.com | www.259635.com | 88051.com | www.682649.com | 019711.com | 723576.com | 500彩票www.51515r.com | www.079921.com | www.360031.com | 645513.com | www.36ez.com | www.kb90.com | www.28077.com | www.98696.cc | www.215128.com | 11423.com | www.166386.com | www.689018.com | 224364.com | 540717.com | www.917744.com | www.2244.biz | www.122847.com | www.271977.com | www.326120.com | www.422665.com | 583426.com | www.122214.com | www.350844.com | www.3nu.com | www.rd37.com | 994010.com | www.632791.com | www.338141.com | www.3169.xyz | 180332.com | www.996609.cc | www.385990.com | www.222415.com | www.zp59.com | www.055680.com | www.8078.cm | www.4345.com | www.vb37.com | www.11nr.com | www.33719.com | www.3113.biz | www.318207.com | www.92db.cc | www.53uz.com | www.864886.com | www.985945.com | www.949814.com | www.hr67.cc | www.60al.com | www.3698.shop | www.34640.com | www.13628.cc | www.289753.com | www.319630.com | www.333653.com | www.365242.cc | www.500599.com | www.740744.cc | www.774022.com | 365812.cc | GO彩www.dao90.com | www.iy4.com | www.mn58.com | www.h73.club | www.028399.com | www.675276.com | www.773907.com | www.462.cn | www.777963.com | 633496.com | 365048.com | www.8213.xyz | www.lz49.com | www.818609.com | www.130310.com | www.9990.vip | www.638520.com | 191405.com | 幸运彩票网www.33598i.com | www.fg59.com | www.9952.org | www.xi49.cc | 317883.com | www.7142.com | www.813218.com | www.888629.com | www.807576.com | 920228.com | www.7802.vip | www.lr88.cc | www.5738.cc | www.79bh.com | www.09652.com | 375432.com | www.031608.com | www.224248.com | www.678171.com | 235244.com | 762523.com | www.34fv.com | www.4655.biz | www.125391.com | www.364062.com | 317609.com | 638165.com | 529767.com | www.020677.com | www.537522.com | www.742299.com | www.891900.com | www.26kv.com | www.1014.net | www.087857.com | www.154499.com | www.474192.com | www.635663.com | www.891521.com | www.019127.com | 933412.com | www.by94.com | www.2yv.com | www.305669.com | www.719152.com | www.737291.com | www.705264.com | 203456.com | www.306083.com | www.6574.cm | www.397782.com | www.972984.com | 如意彩票www.938518.com | www.99.me | www.xy16.com | www.501720.com | www.712.cm | www.8258.cn | www.547574.com | www.902632.com | www.817989.com | www.656857.com | www.439915.com | www.259907.com | www.681885.com | www.508738.com | www.315938.com | www.801552.com | www.808327.com | www.705397.com | www.654070.com | www.896617.com | www.682120.com | 292512.com | www.140533.com | www.187333.com | www.520958.com | www.528898.com | www.392796.com | www.682499.com | www.605936.com | www.361552.com | 944966.com | www.868827.com | 449223.com | www.909554.com | www.873464.com | www.9265.xyz | www.5000.tv | www.064014.com | www.336621.com | www.005451.com | 全民快乐8www.qmkl1.com | www.718257.com | www.010084.com | www.793013.com | www.9505.cc | 977806.com | www.521493.com | www.335039.com | 大赢家彩票平台www.902257.com | www.340.bid | www.74qv.com | www.31170.com | www.98653.cc | www.917283.com | www.622051.com | www.662602.com | 506278.com | www.cai1044.com | 公益福彩www.gyfc1.com | 714823.com | www.1302.vip | www.9999.mobi | www.38xw.com | www.369474.com | www.39262.cc | 594570.com | www.896987.com | www.177398.com | www.42wg.com | www.16365.com | www.25851.cc | www.09066.com | www.81sg.com | k3k3彩票www.602742.com | www.ru17.com | ag31.cc | www.977406.com | www.797036.com | www.629066.com | www.383969.com | www.832071.com | 8k彩票www.803242.com | www.69pu.com | www.27eu.com | www.06ah.com | www.1170.cc | www.255273.com | www.552999.com | www.999652.com | www.969442.com | www.658612.com | 209660.com | 066013.com | 299733.cc | 141819.com | 922098.com | www.169807.com | www.623.blue | 567054.com | www.120589.com | www.091728.com | 天天中彩www.950606.com | www.210554.com | www.369462.com | www.702086.com | www.630979.com | www.675855.com | www.529665.com | 326282.com | www.789192.com | www.200955.com | www.60ke.com | www.967949.com | www.1922.vip | www.63223.cc | www.223652.com | www.225702.com | www.320122.com | www.505139.com | www.513973.com | www.520608.com | www.871681.com | www.867997.com | www.811029.com | 303488.com | www.984482.com | www.769207.com | 914566.com | 45uf.com | 748182.com | www.964767.com | 604430.com | 358741.com | 626693.com | 220368.com | www.908818.com | 225460.cc | 643355.com | www.1863.live | www.133559.com | www.389706.com | www.804039.com | www.28269.cc | www.127554.com | www.593911.com | www.803999.cc | 750660.com | www.826604.com | www.593303.com | www.007345.com | 980351.com | www.586202.com | www.166924.com | 884887.com | 769743.com | 975451.com | www.nh61.com | www.d54.xyz | www.00os.com | 彩客网www.595707.com | 975306.com | 137409.com | 525534.com | 627906.com | 093522.com | www.915001.com | www.633939.com | 268917.com | 731944.com | www.968884.com | www.986245.com | kj30.com | www.az67.com | www.rr1.cc | 143677.com | 069564.com | 505699.com | www.984120.com | 535700.com | 026471.com | www.977390.com | 900613.com | 395715.com | 979414.com | 759469.com | 237141.com | www.rw8.cc | www.mu43.com | www.fn5.cc | 815739.com | 15un.com | 755602.com | 616131.com | 04ic.com | 937027.com | www.971947.com | 343824.com | 凤凰彩票www.77803z.com | 09920.com | www.cp267.cc | 881943.com | 047110.com | 267993.com | 585450.com | 333875.com | 47169.com | 385536.com | www.916824.com | www.817187.com | www.894732.com | www.698222.com | www.731441.com | www.664369.com | www.917013.com | www.951061.com | 898327.com | 03855.com | www.973210.com | www.842978.com | 292579.com | www.966823.com | www.737303.com | 978224.com | 078076.com | 567034.com | www.545206.com | www.294336.com | www.680216.com | www.877789.com | www.922179.com | www.586202.com | www.313619.com | www.665843.com | www.070685.com | www.084585.com | www.69ki.com | www.04673.com | www.385218.com | www.814421.com | www.813311.com | 187099.com | 254737.com | 142699.com | 090386.com | 384512.com | www.930638.com | www.876287.com | www.973361.com | www.951676.com | www.704502.com | www.705229.com | www.502389.com | www.279351.com | www.717925.com | www.961424.com | 878058.com | 539824.com | 587031.com | cp2043.com | 063216.com | www.2hq.cc | 众乐彩票www.689144.com | 808361.com | 976140.com | www.986708.com | 026431.com | www.927003.com | www.750498.com | www.938569.com | www.767993.com | www.827008.com | www.886097.com | 358389.com | 907770.com | www.891057.com | 812597.com | www.310385.com | 386517.com | 701091.com | www.826361.com | www.553896.com | 562591.com | www.502259.com | www.68201.com | 658152.com | 721799.com | www.318639.cc | www.x87.cc | www.819911.com | www.963.cm | www.037111.com | www.296372.com | www.954043.com | www.771913.com | www.848242.com | www.770770.com | www.865527.com | www.982323.com | www.954380.com | www.976431.com | www.680271.com | 447302.com | 113354.com | 074633.com | www.865019.com | www.21wq.com | www.83qw.com | www.ri01.com | www.02pt.com | www.4380.in | www.31179.com | www.053516.com | www.346980.com | www.299629.com | www.4970.cn | www.51ls.cc | www.8265.cc | www.578384.com | www.862278.com | www.678247.com | www.582253.com | www.853382.com | www.874693.com | 895402.com | www.93je.com | www.341188.com | www.128784.com | www.96558.com | www.99771.com | www.506041.com | www.822531.com | 284327.com | www.991804.com | 358144.com | www.298866.com | 514079.com | 935641.com | www.948851.com | www.700065.cc | www.754948.com | www.888163.com | www.356692.com | www.125484.com | 彩之家www.10czj.com | www.593535.com | www.328004.com | www.mx92.com | www.899985.com | www.139901.com | www.728.tv | 556648.com | www.35222.com | www.345886.com | www.42ue.com | www.811403.com | www.is92.com | www.64rx.com | www.052759.com | www.1997.mobi | www.86iy.com | www.1234.org | www.66305.com | www.051266.com | www.84538.com | www.52381.cc | www.153406.com | www.85632.cc | www.05993.com | www.9255.com | www.52396.cc | www.3059.cm | www.m30.me | www.cai5671.com | 397633.com | 397594.com | www.8570.loan | www.200474.com | www.115705.com | www.45240.com | www.421977.com | www.771115.com | 317644.com | 965794.com | 953914.com | www.919497.com | www.686800.cc | www.882764.com | www.796772.com | www.703779.com | www.960727.com | www.390311.com | www.202944.com | www.627955.com | 26fs.com | www.63vt.com | www.ed48.com | www.sq85.com | 231197.com | 804616.com | www.6uu.com | 幸运彩票www.768299.com | 660282.com | 586524.com | 764802.com | www.858985.com | www.551633.com | www.550221.com | www.400752.com | www.276708.com | www.473609.com | www.273467.com | www.588066.com | www.333253.com | www.151851.com | www.215930.com | www.059832.com | www.33623.cc | www.9258.biz | www.20sb.com | 984739.com | 024199.com | www.972451.com | www.969735.com | 140043.com | 680532.com | www.954581.com | www.739955.com | www.552298.com | www.303075.com | www.119605.com | www.8546.vip | 501285.com | 702875.com | 979042.com | www.959649.com | www.958431.com | www.739625.com | 107016.com | www.773239.com | 006927.com | www.774576.com | www.948857.com | 445770.com | www.835510.com | 075002.com | www.906933.com | 406217.com | 909915.com | www.994192.com | 484829.com | 39jh.com | 356705.com | 506810.com | www.766444.com | www.42286.com | 9896.net | www.376430.com | www.029741.com | 8号彩票www.60108y.com | 9070.biz | 029377.com | www.906967.com | www.919545.com | www.703970.com | www.558645.com | 480199.com | 500彩票www.701540.com | www.653010.com | www.9093.cc | 032116.com | www.293731.com | 390920.com | 967664.com | www.816566.com | www.706329.com | www.986681.com | www.688561.com | www.393771.com | www.269771.com | www.539117.com | www.397051.com | www.562061.com | www.752356.com | www.97593.com | 372079.com | www.571510.com | www.3078.pw | 951045.com | www.353628.com | www.951303.com | www.501652.com | www.044558.com | www.27qb.com | 707926.com | www.811585.com | www.974459.com | 078958.com | 740050.com | 422441.com | www.825828.com | www.649494.com | www.911595.com | 717210.com | 乐彩赢www.0014u.com | www.948380.com | www.066832.com | www.8gc.cc | www.206387.com | www.73258.com | www.266552.com | www.64yf.com | www.910342.com | 848771.com | 936902.com | www.791072.com | www.604514.com | www.761922.com | www.659497.com | www.844844.com | www.733959.com | www.919902.com | www.746676.com | www.461562.com | www.564196.com | www.623072.com | www.382014.com | www.433904.com | www.984623.com | www.938219.com | www.734308.com | www.459299.com | www.771528.com | www.503038.com | www.268218.com | www.567515.com | www.989094.com | www.917558.com | www.660909.com | www.619949.com | www.671186.com | www.435254.com | www.579765.com | www.281185.com | www.8099.cc | www.0746.org | www.gk09.com | 415116.com | 363177.com | 500彩票网www.61655f.com | www.873907.com | www.30fs.com | www.7445.top | www.024221.com | www.247922.com | www.037236.com | www.234868.com | www.127444.com | www.46358.com | www.41266.com | www.vu16.com | 376172.com | 809325.com | www.841932.com | www.480274.com | 380788.com | www.911690.com | www.607328.com | www.446368.com | www.128745.com | www.96jw.com | www.09tn.com | 创世纪彩票www.36787g.com | 859884.com | xr03.com | 908322.com | www.752908.com | www.246394.com | www.038897.com | www.705928.com | www.761426.com | www.511749.com | www.268445.com | www.020935.com | www.5031.live | www.61rn.com | www.cp5738.com | 309928.com | www.897605.com | www.568788.com | www.320853.com | www.671497.com | www.592820.com | www.335073.com | www.526026.com | www.328897.com | www.323961.com | www.292669.com | www.676571.com | 437622.com | 彩82www.c9337.com | 690416.com | 08970.com | qm10.com | www.649177.com | www.767166.com | 444494.com | www.757781.com | www.626979.com | www.545399.com | www.122134.com | www.1608.pw | www.87np.com | 网易彩票www.163136.com | 180331.com | www.946662.com | www.480223.com | www.721036.com | www.564719.com | www.393389.com | www.321590.com | www.39263.cc | 500彩票www.50074f.com | www.995605.com | 364960.com | www.853330.com | www.753627.com | www.729195.com | www.963852.cc | www.625009.com | www.660465.com | www.590763.com | 4079.biz | www.948163.com | 518380.com | 665416.com | www.775252.com | www.951439.com | 554680.com | www.778223.com | www.860104.com | www.525727.com | www.36pz.cc | www.548732.com | www.276231.com | www.2254.com | www.12662.com | www.8731.xyz | www.58om.com | 大赢家彩票www.493381.com | 439904.com | www.976126.com | www.919123.com | www.903830.com | www.858254.com | www.887551.com | www.644624.com | www.068233.com | www.104293.com | www.019966.com | 华人彩票www.hr0888.com | www.79jh.com | 822050.com | www.zl75.com | 957834.com | 123007.cc | www.678897.com | www.391073.com | www.493163.com | www.101913.com | www.8172.xyz | www.4527.cn | www.6699.biz | 397864.com | 500彩票网www.97655t.com | 428784.com | www.825292.com | www.668618.com | www.555584.com | www.588499.com | www.885905.com | www.517526.com | www.397704.com | www.315349.com | www.201713.cc | www.511893.com | www.559448.com | www.217597.com | www.73755.com | www.18906.com | www.56ww.com | www.93xl.com | 乐彩赢www.0014z.com | www.ty5.com | www.zs98.com | www.da53.com | 997194.com | 983064.com | 225108.com | www.629167.com | www.505754.com | www.184855.com | www.622096.com | www.761451.com | www.844543.com | www.710628.com | www.350939.com | www.108899.cc | www.313999.cc | www.80670.com | www.14927.com | www.cai100.com | 365635.cc | www.845196.com | www.539674.com | www.855126.com | www.672122.com | www.660698.com | www.748688.com | www.696525.com | www.903443.com | www.590385.com | www.492790.com | www.358163.com | www.416965.com | www.107277.com | www.hx90.cc | 100224.com | 106831.com | www.812089.com | www.567246.com | www.201910.com | www.198404.com | www.77499.com | www.93us.com | www.911723.com | www.939759.com | www.047182.com | www.6378.cm | 234071.com | www.899279.com | www.507173.com | www.332940.com | www.615377.com | www.446227.com | www.660693.com | www.623076.com | www.554632.com | www.197873.com | www.4481.cn | www.ed9.com | 930195.com | www.9