全合成全套抗體庫(kù)的構(gòu)建.pdf

1、原創(chuàng)性聲明本人鄭重聲明:所呈交的學(xué)位論文，是本人在導(dǎo)師的指導(dǎo)下，獨(dú)立進(jìn)行研究所取得的成果。除文中已經(jīng)注明引用的內(nèi)容外，本論文不包含任何其他個(gè)人或集體已經(jīng)發(fā)表或撰寫(xiě)過(guò)的科研成果。對(duì)本文的研究作出重要貢獻(xiàn)的個(gè)人和集體，均已在文中以明確方式標(biāo)明。本聲明的法律責(zé)任由本人承擔(dān)。論文作者簽名日期:g.8生As二21關(guān)于學(xué)位論文使用授權(quán)的聲明本人完全了解山東大學(xué)有關(guān)保留、使用學(xué)位論文的規(guī)定，同意學(xué)校保留或向國(guó)家有關(guān)部門(mén)或機(jī)構(gòu)送交論文的復(fù)印件和電子版，

2、允許論文被查閱和借閱本人授權(quán)山東大學(xué)可以將本學(xué)位論文的全部或部分內(nèi)容編入有關(guān)數(shù)據(jù)庫(kù)進(jìn)行檢索，可以采用影印、縮印或其他復(fù)制手段保存論文和匯編本學(xué)位論文。(保密論文在解密后應(yīng)遵守此規(guī)定)論文作者簽名:導(dǎo)師簽名二Ib魚(yú)0。:a.Q生些州山東大學(xué)碩士學(xué)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