?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F39822%2F&rft.title=Optochemical+Approaches+for+Controlling+Protein+Dimerization+and+Protein+Function&rft.creator=Courtney%2C+Taylor&rft.description=Light+activation+of+small+molecules%2C+peptides%2C+and+proteins+is+a+useful+tool+for+the+precise%2C+spatiotemporal+control+of+various+biological+processes.+The+incorporation+of+light-responsive+amino+acids+into+proteins+in+cells+and+organisms+with+an+expanded+genetic+code+has+enabled+the+precise+activation%2Fdeactivation+of+numerous%2C+diverse+proteins%2C+such+as+kinases%2C+nucleases%2C+proteases%2C+and+polymerases.+Herein%2C+I+describe+my+contributions+toward%3A+(1)+the+application+of+genetically+encoded%2C+photo-activatable+cysteine+and+lysine+derivatives+for+improved+understanding+of+the+Ras%2FRaf%2FMEK%2FERK+pathway+(specifically%2C+using+the+dual-specificity+phosphatase%2C+MKP3)+in+mammalian+cells%2C+(2)+the+development+of+a+site-specific+light-induced+oxidation+approach+for+targeted+protein+inactivation%2C+and+(3)+development+and+application+of+new%2C+photoswitchable+amino+acids+for+future+use+in+controlling+metal+complex+formation.%0D%0AIn+addition+to+the+regulation+of+protein+function+using+light-controlled+amino+acids%2C+I+have+contributed+to+the+development+of+photo-controlled+small+molecules+for+manipulating+protein+dimerization.+Rapamycin+is+a+small+molecule+which+dimerizes+two+proteins%2C+FKBP+and+FRB%2C+and+has+been+applied+for+the+conditional+control+of+protein-protein+interactions.+To+provide+additional+levels+of+control%2C+three+different+approaches+were+developed+and+applied+in+this+thesis%3A+(1)+red-+shifted+caged+rapamycin+analogs+for+light-activation+of+dimerization%2C+(2)+ROS-generating+analogs+for+light-inactivation+of+the+ternary+complex%2C+and+(3)+photoswitchable+analogs+which+undergo+a+configurational+change+to+allow+for+preferential+ternary+complex+of+one+isomer+over+another.+The+development+of+these+various+optically+controlled+dimerizers+expands+the+range+of+tools+available+to+chemical+biologists+for+conditional+control+of+protein+dimerization.&rft.date=2021-01-20&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F39822%2F19%2FCourtney%2520Final%2520ETD.pdf&rft.identifier=++Courtney%2C+Taylor++(2021)+Optochemical+Approaches+for+Controlling+Protein+Dimerization+and+Protein+Function.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++