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噬菌体展示技术及其应用.pdf

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1、DZ,2008,29(1): 60-63Progress in Veterinary Medicine )8Z U/ # *刘相叶,邓洪宽,吴秀萍,王学林,于申业,于艳玲,刘明远*( v $ uD u h L i, =130062)K 1:噬菌体展示技术是一项新兴的分子生物学技术;该技术将基因型和表现型有效地联系起来,是后基因组时代的有力工具b目前用于构建展示文库的噬菌体主要有丝状噬菌体aK噬菌体aT4噬菌体和T7噬菌体;它们所展示的外源蛋白可以保持相对独立的空间结构和生物活性b随着此项技术的不断完善和发展,噬菌体展示技术已在新型疫苗的研制a酶抑制剂的筛选a医学诊断和治疗a多肽药物的开发a蛋白

2、质相互作用的研究等领域得到了广泛的应用,并显示了良好的应用前景b1oM:噬菌体展示技术;原理;应用ms |:Q782DS M : AcI|:1007-5038( 2008) 01-0060-041985 M, SMissourivSmith G P1 nQ L )8fdyF ?YVy m/, EcoR = M sy )8Q1I Tp ( protein )y ,F )8 ?$ FEcoR = M F8 MY,Ny )8Z U/ ( phage displaytechnology )b )8Z U/ ?|Vrt TZ U )8V ,7YV T“E Vr+st )82 , “t $b1 )8Z U

3、/ )8Z U/ |DNAYVy/ X H a )88 , PDNA Vr )8I T ,C )8V ,$Z UtV M bW 3b s0, a!ZE! d+s )8,KV )8 o ?s0 “ )8;tVr )8V ,7 I yT )8yFBs VYV )8DNA b/ A+ y yVCW1“b2 )8Z U“d 2.1 丝状噬菌体展示系统 )8 DNAh,I 10, )8Z U1 p p ITbp )8 R B ,35 J, VN aN N C u tbpZ UtvlK,p J 3 5, f 3f s Kbp )8 R ,BN N bp s0 l, ? lt ,ztvY TF , P b

4、J,yN“dB T 8, Jp f 7? .Nb2.2 K噬菌体展示系统K )8 K* P X H8, LDNA, 12 bK )8Z U“d | )8hF ADN C ,1PV | u(d ? u), LCV Z UbK )8 % =,|ts % ) , VZUvs0( 100 ku )# %, aSSOCT4yF,4 ) 3G )8, V|t/Z U )8V bSOC )8 R V B ? ,yN V8F ZE LCZ UbZE |SOC# 3v )Vr, s ,B,F SOC )8 R h, VrZ U “bT4 )88V8FO“d v( 35 ku ), J , C,N ? a,7 P

5、 3 s Kb2.4 T7噬菌体展示系统T7 )8I TY T,10A(344 )10B( 397 ),+10BI T ui )8V , $T )8Z UbZ UT7 )8V t1YV% s ,y7 V Z UtS M=: )8Z U/ # o,| M1 k47/ HqbMachold K P11-12 )8Z U/ VrB ? y0( tumor necrosis factor, TNF)4,|N4 4 (refractory a-nemia,RA), P 0, A b )8t oVr F8 “V e V zT,4 rT,b S: F8 V P ?_ b3.4 在多肽药物开发中的应用 )8Z

6、 Ut/ ? t/ “M ?, N+,? + ? Os0 )8Z U o,B ?s0 , VeL y s0 ,.s5 = 3y0yFT7 )8f l LewiskT J.,2006, 25(10): 1221-1226.6 Dennis M S, Eigenbiot C, Skelton N J, et al. Peptide exoxiteinhibitors of factor a as anticogulants J. Nature, 2000,404(6777): 465-470.7 Ev, XK.V )8t o A- $ 4J. 3 3 , 2001, 33(5): 513-518.

7、8 Deng S, Xu Y, Liu R, et al. M imic epitope of aflatoxin B1screened by phage display technique J. Wei Sheng Yan Jiu,2007, 36(1): 59-62.9 Tordsson I M, Ohlsson L G, Ilbrahmsen L B, et al. Phage-se-lected primate antibodies fused to superantigen for immuno-therapy of malignant melanoma J. Cancer Immu

8、nol Immu-nother, 2000, 48(12): 691-702.10 , O ,(!,. )8 15t o SLEM1t J. 3 f,2001, 21(3): 275-277. 11 Machold K P, Smolen J S. Adalimumab-a new TNF-alpha an-tibody for treatment of inflammatory joint diseaseJ. ExpertOpin Biol Ther, 2003, 3(2): 351-360. 12 Taylor P C. Ant-iTNFalpha therapy for rheumato

9、id arthritis:an update J. Intern Med, 2003, 42(1): 15-20.13 Ferrer M, Harrison S C. Peptide ligands to human immunod-eficiency virus type1gp120 identified from phage display l-ibrariesJ. Virology, 1999, 73(22): 5795-5820.14 Delano W L, Ultsch M H, de Vos A M, et al. Convergentsolutions to binding at

10、 a protein-protein interfaceJ. Science,2000, 287(10): 1279-1283.15 Takagi T, Arisawa T, Yamamoto K, et al. Identification ofligands binding specifically to inflammatory intestinal mucosausing phage displayJ. Clin Exp Pharmacol Physiol, 2007,34(4): 286-289.16 Xu L, Jin B Q, Fan D M. Selection and ide

11、ntification of mim-ic epitopes for gastric cancer associated antigen MG7-AgJ.Cancer Ther, 2003, 2(3): 301-306.17 Romanov V I, Durand D B, Petrenko V A. Phage display se-lection of peptides that affect prostate carcinoma cells attach-ment and invasionJ. Prostate, 2001, 47(4): 239-251.18 Zhang Y, Chen

12、 J, Zhang Y, et al. Panning and Identificationof a Colon Tumor Binding Peptide from a Phage Display Pep-tide LibraryJ. J Biomol Screen, 2007, 12(3): 429-435.19 Pillutla R C, Hsiao K C, Beasley J R, et al. Peptides identifythe critical hotspots involved in thebiological action of the in-sulin recepto

13、rJ. J BiolChem, 2002, 277(25): 22590-22594.20 Hsiao K C, Brissette R E, Wang P, et al. Peptides identifymultiple hotspots within the ligand binding domain of theTNF receptor 2J. Proteome Sci, 2003, 1(1): 1-10.21 ,f,f ,.T7 )8Z U/ HCVMT J. +Dv,2007, 29(10): 876-878.22 ,f , ,.T7 )8Z U/ YhPreS1MT J. iD

14、Sv, 2007,32(4): 340-343.Phage Display Technology and Its ApplicationLIU Xiang-ye, DENG Hong-kuan, WU Xiu-ping, WANG Xue-lin,YU Shen-ye, YU Yan-ling, LIU Ming-yuan(Key Laboratory of Zoonoses, Ministry of Education of China, College of A nimalScience and Veterinary Medicine, Jilin University , Changch

15、un, Jilin, 130062, China)Abstract: Phage display technology is a new molecular biology technique,which can effectively linked geno-type and phenotype in a same body, is and become a powerful tool in the post-genome era. Currently, themain phage used to build phage display library includes filamentou

16、s phage,Kphage, T4 phage and T7 bac-teriophage. The exogenous protein that was displayed can also keep relative independent activity in thespatial structure and biological activity. With the improvement and development, this technique has beenused widely in the development of new vaccines, the enzyme inhibitor screening, medical diagnosis andtreatment, peptide drug development, protein interaction and so on. Furthermore, it has demonstrated agood prospect.Keywords:phage display technology; principle;application63 M=: )8Z U/ #

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