Date Approved

2019

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Committee Member

Hedeel Evans, PhD

Committee Member

Deborah Heyl-Clegg, PhD

Committee Member

Jeffery Guthrie, PhD

Abstract

Dopamine receptors D1R and D2R form a heterooligomeric complex with signaling properties distinct from the individual receptors. Aberrant expression of this protein-protein complex is linked to the etiology of various neuropsychiatric diseases. Formation of the D1R-D2R heteromer is thought to be dependent upon electrostatic interactions occurring between the carboxyl tail of D1R and the third intracellular loop of D2R. Using this interaction site as template, I synthesized several peptides designed to disrupt the minimal area of the D1R-D2R interaction interface and tested these using whole cell lysates of human brain tissue and dopamine receptor constructs. I report that a synthetic peptide with the sequence EAARRAQE is efficient in blocking D1R-D2R interaction, while shorter and more highly charged peptides (EERRAQ, ARRA and AARRAQ) had no effect. This research provides insight into the binding regions involved in D1-D2 heteromer formation, and may aid future drug development efforts that target this receptor complex.

Included in

Biochemistry Commons

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