Synthesis of exo-affinity labeling agents of protein tyrosine phosphatase non-receptor type 1

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Protein-tyrosine phosphatase 1B (PTP1B) is a negative regulator in the insulin signaling cascade. A lot of research has focused on inhibiting PTP1B but with no success. Only one drug is currently in phase II clinical trials. We have developed a synthetic protocol to create a library of molecules that target residues outside the active site and covalently bind to the enzyme via close proximity alkylation. These molecules will be analyzed towards inactivation/inhibition capabilities. Tirapazamine is a hypoxia selective anti-cancer drug. New derivatives of Tirapazamine are sought after. We have analyzed and optimized Suzuki-Miyaura and Buchwald-Hartwig couplings reactions towards new derivatives of Tirapazamine. Allyl isothiocyanate (AITC) is a phytochemical that can be found in cruciferous vegetables and has received interest due to beneficial health effects. During our analyses of AITC towards inactivation of PTP1B we noticed the surprising absence of the isothiocyanate carbon in 13C NMR spectra. Calculations show that the absence is due to the facile change of the N-hybridization in the wide range of 120 less than 180 bond angles in AITC.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemistry (MU)

Grantor dc:publisher

University of Missouri--Columbia

Year dc:date.issued

2015

Author dc:creator

• Hillebrand, Roman

Advisor dc:contributor.advisor

• Gates, Kent S. (Kent Stephen), 1962-

Statement dc:rights

• Access to files is limited to the campuses of the University of Missouri with SSO login.

Language dc:language.iso

eng, English

DOI

https://doi.org/10.32469/10355/47070

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/47070