Neurotensin (NT) is an endogenous 13 amino-acid long neuropeptide. NT acts on both the central and peripheral nervous system against three known receptors, neurotensin receptors (NTSR) 1,2 , and 3. NTSR1 and NTSR2 are G-protein coupled receptors and have been proposed as therapeutic targets for many human disease states. Specifically, there has been interest in developing antipsychotic therapeutics that act through the activation of NTSR1 in the central nervous system in addition to, the development of cancer therapeutics and diagnostics that target peripheral NTSR1. Additionally, there has been great interest in the use of macrocyclic peptide analogues as some macrocycles have been shown to be orally bioavailable, promote receptor selectivity, and resist protease degradation. Here I use computational ligand docking and molecular dynamics to explore the design of novel macrocyclic neurotensin analogues. Furthermore, I will comprehensively characterize the binding and signalling properties of my macrocycles in cell-based assays.