Date of Award

5-2024

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Giovanni Gadda

Second Advisor

Jenny Yang

Third Advisor

Ming Luo

Fourth Advisor

Kostiantyn Marichev

Abstract

Calcium is a universal messenger that regulates many biological and pathological processes by interacting with crucial calcium-binding proteins like the calcium-sensing receptor (CaSR). CaSR is a prominent protein that regulates various signaling pathways and diseases and detects changes in extracellular calcium concentration and metabolites to cause calcium changes in the intracellular environment. The study detailed in this thesis elucidates CaSR's presumed function in calcium homeostasis regulation and explores the binding and functional cooperativity of bacterially expressed CaSR using Trp-sensitized FRET assay. The second section of this thesis explores the optimization of TNCA a natural allosteric modulator of CaSR as our lead compound with the aid of structure-based drug design to develop novel CaSR therapeutics.

These investigations offer valuable insights into the molecular basis for CaSR-related diseases to facilitate the discovery of new therapeutics.

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