Page 94 - Tyrosine-Based Bioconjugations - Jorick Bruins

Chapter 5
ns 5.6. Conclusions
oped various nWoveehl mavethdoedvesltoopeadntvibaoridoyu-sprnotveeinl mcoenthjuogdastetos baansteibdoodny-sptreopt-ewinisceonjugates based on step-wise razine ligation (SfPoOr CmQonaonfdutnecttriaozninaleizlaigtiaotnioonf(afonrtimbodnyo)fourncbtyiofnuartlhizearticoonmobf iannatiboondy) or by further combination -based protweiitnh csonrjtuagsea-tbioansed (fopr rotediinfunctcionjaulgizatiion). (foSrpecifdicifaullnyc, tionalization). Specifically, lization was acmhioenvoefdunbcatsieodnaolnizatitownow-satasgaechaipepvreodacbhasetdarotingawtwitoh-isntatrgoedaupcptiroonach starting with introduction y based on chemofoaseTlCeOctmiveoiSePtyObCaQsewditohnacBhCeNm-oPsEeGle3-cTtCivOelSinPkOeCrQ, awfteitrhwahBiCchNI-EPDEGDA3-TCO linker, after which IEDDA ed for attachmecannt obfeaeMmepTlozy-beedafroinr gatptraocthemine,notliogfoanuMcleTozt-ibdea, roinr gsmpraolltmeino,leocluigloen. ucleotide, or small molecule. hese moieties Tfoastinetrroadnudcme othreseffmicoieinetiley,s iftawstaesr faonudndmothreatetfhfiecielenntglyt,hitofwtahsefound that the length of the between the apnetipbtoidey sapnadcethr ebeGt4wY-eteang tphlaeyasnaticbroudcyiaal nrodlethine tGh4eY-etfafgicpielanycsy aofcrtuhceial role in the efficiency of the rticular with rergearcdtioton,oixnidpaatriotincuolafrthweitthermegianradl tyorosxiindeatrieosnidoufethbey tmeTrmyri,nwalithyrosine residue by mTyr, with
(G4S and G4SG4lSo)nsgiegrnisfpicaacnetrlsy(sGp4eSeadnindgGu4pSGth4Se)esfigfinciefincacnytolyf tshpeeredaincgtiounp.the efficiency of the reaction.
conjugation mTehthisodtwwo-astespubcsoenqjuegnatiloynfumrtehtehrodexwteansdesudbtsoeqtuhengtleynfeurratthioenr eoxftended to the generation of tibodies with htriigfhunecftfiocineanlcayn. tIinbothdisescawseit,hahfiigrhstepfrfioctieincyis. iInttrhoidsucaesde,basfeirdstopnrotein is introduced based on n followed by sIoEDrtDasAe, alingadtiaonsefcoollnodwepdrobteyinIEvDiDa AS,PaOnCdQafoslelocowned pbryotIeEiDnDvAia. ISnPOCQ followed by IEDDA. In ave shown thadtdtihtieonv,awleenchyaovef tsheowrensutlhtaintgthtreifuvnacletinocnyalofantthiebordeiseusltcinagn tbreifunctional antibodies can be ed towards eithcearedfualllydtiavialolernedt ftuonwcatirodnsaeliiztahteior nduoanl bdoivtahlelingthftuanncdtiohnealvizyacthioaninosn, both light and heavy chains, alent functionaolirzadtuioanl mononoorvtawleonstrfucntcutrioanllyaldiziastinocntohneaovrytwchoasintrsu.cOtuthraelrlyfodrimstaintcst heavy chains. Other formats ntibody ratios hoarvperobtecino-mtoe-annotiboedeynrinatvieostihgavtedbehceorem,ebuntoatrbeeoebnviinovuessltyigaalstoedathere, but are obviously also at
hand.
al tests with theWbhi-ilaenfduntrcitfiuoncatliotensatlsawntitibhothdeiebsip-raensdentrtiefudnhcetrioeninalaarentoibnogdoiensgp(breustented herein are ongoing (but resenting), weneont vriesaiodny tfhoer pgreensernatiinogn),owf etriefunnvicstiionathl eangteibnoedraietsioin oafmtroifduunlcatrional antibodies in a modular ow for rapid prfoadsuhciotinonwiollfablilsopwecfoifricrAapDiCdsporrodimucmtiuonoocfytboiskpineecsif,icasAwDeClsl oasr imamnyunocytokines, as well as many ng multifunctionthaleranintitbeoredsyticnognmstruultcitfsu.nTcthiiosnwalillanetnibaboldeytchoenrsatrpuidcts.crTeheinsinwgilloefnable the rapid screening of fics based on e.vga.raynintigbenisptaercgifeicts,blianskedr otynpe.sga. nandtliegnegntthasr,gaentds,dlinffkeerretnytppeasyalonaddlsengths, and different payloads
targeting and tsoubimsepqruoevnetcterlel atatmrgentitn. g and subsequent treatment.
ng informatio5n.7. Supporting information
Information isTahveaSiluapbpleofrrteinegoIfncfohramrgaetiaotntihseaevnaidlaobflethfirseme oanf uchscarigpet.at the end of this manuscript.
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