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Development of Optical Tools to Control Biological Processes

Horst, Trevor (2019) Development of Optical Tools to Control Biological Processes. Master's Thesis, University of Pittsburgh. (Unpublished)

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Optical control of protein function has garnered considerable interest in chemical biology. The use of light to modulate protein function allows for higher spatial and temporal control than small molecule control. Rapamycin is a natural product that can be used to induce the dimerization of FKBP and FRB proteins and has been used as a small molecule to control a wide range of dimerization-based protein functions. We synthesized several light sensitive analogs of rapamycin to allow for optical control of protein dimerization. A visible light-activated rapamycin analog was synthesized and its ability to effectively photocage rapamycin in vivo was demonstrated. A light-deactivated rapamycin analog was synthesized through the conjugation of a reactive oxygen species generating chromophore to rapamycin in an adaption of chromophore-assisted light inactivation of proteins. The ability of this conjugate to reverse protein dimerization was demonstrated in vivo as well. Several analogs of rapamycin conjugated to arylazopyrazole and spiropyran photoswitches were synthesized and the difference in dimerization activity of the two states was determined. Optical control of protein function was also explored through the incorporation of photoswitching amino acids through unnatural amino acid mutagenesis. Two novel photoswitching amino acids containing arylazopyrazole and phenazopyridine photoswitches were synthesized, and incorporation in proteins was demonstrated.
Optically active materials have been a focus of researchers developing robotics, information storage methods, and light-activated drug delivery. Commonly, azobenzene is used in these materials. We synthesized an arylazopyrazole-containing monomer capable of being incorporated into a polymer. Analysis of that polymer showed an unexpectedly lesser macroscopic response to irradiation than an azobenzene containing material.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Horst, Trevortjh84@pitt.edutjh84
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairDeiters, Alexanderdeiters@pitt.edudeiters
Committee MemberIslam, Kabirulkai27@pitt.edukai27
Committee MemberFloreancig, Paulflorean@pitt.eduflorean
Date: 21 June 2019
Date Type: Publication
Defense Date: 26 March 2019
Approval Date: 21 June 2019
Submission Date: 11 April 2019
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 133
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Chemical Biology, Rapamycin, Organic Synthesis
Date Deposited: 21 Jun 2019 18:10
Last Modified: 21 Jun 2021 05:15

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