全合成全套抗體庫的構建.pdf

1、原創(chuàng)性聲明本人鄭重聲明:所呈交的學位論文，是本人在導師的指導下，獨立進行研究所取得的成果。除文中已經注明引用的內容外，本論文不包含任何其他個人或集體已經發(fā)表或撰寫過的科研成果。對本文的研究作出重要貢獻的個人和集體，均已在文中以明確方式標明。本聲明的法律責任由本人承擔。論文作者簽名日期:g.8生As二21關于學位論文使用授權的聲明本人完全了解山東大學有關保留、使用學位論文的規(guī)定，同意學校保留或向國家有關部門或機構送交論文的復印件和電子版，

2、允許論文被查閱和借閱本人授權山東大學可以將本學位論文的全部或部分內容編入有關數(shù)據庫進行檢索，可以采用影印、縮印或其他復制手段保存論文和匯編本學位論文。(保密論文在解密后應遵守此規(guī)定)論文作者簽名:導師簽名二Ib魚0。:a.Q生些州山東大學碩士學位論文AbstractAntibodiesarethemostcomplexmoleculesinthebodiesofvibrateincludinghumanbeings.Theyhavegr

3、eatdiversitybecauseoftheirspecificgenestructuresandrecombinationmodelswhichenablethemtoefectivelyprotectthebodies.Soantibodiesareplayinganimportantroleinclinicalanddiagnosesandaccordinglythedevelopmentofthetechniquesofan

4、tibodyhavealwaysbeenattractingscientistseyeballs.Techniquesofantibodyhavealwaysbeenatractingscientistseyeballs.Nowadaysantibodiesusedinmedicinesderivemainlyfromanimalsandthesenonhumanantibodiscanhaveagoodcurativeefectina

5、cuteinfectionortoxicosisbutrepeatedusewillleadtobodysrejectionwhichundoubtedlyrestrictstheirapplication.Onewayoutistousehumanizedantibodiestoreplacenonhumanantibodies.Thetechniquesforengineeringantidiesaregoodchoicestoth

6、istarget.Usingengineeringtechniquespeoplecanchangetheformsofantibodiesandevencreatenewkindsofantibodieswhichdonotexistnatrually.Generallyengineeringtechniqueincludestechniqueofhumanizationofmousederivedantibodytechniqueo

7、fsmallmoleculeantibodiestechniqueoftransgenedmouseandtechniqueofantibodylibraryamongwhichthelastoneismostpowerfulandmostatractive.Inthispapertheconstructionofafullysynthetichumancombinatorialantibodylibraries(HuCAL)based

8、onmodularconsensusframeworksandCDRsrandomizedwithtrinucleotidesisisdipictedwithVH3x3asanexample.Thefollowingarethesteps:firstanalyzingthehumanantibodyrepertoireintermsofstructureaminoacidsequencediversityandgermlineusage

9、andso14modularconsensusframeworkswhichcomefrom14germlinefamiliesareabstracted(heavychain7kappachain4andlamdachain3).IntheframeworksthesectionsoftheCDRsarereplacedwithdummysequences.SecondthecodonsusedfrequentlyinEcoliare