Master of Science (MS)
Jered C. Garrison, Ph.D.
Nicholas T. Woods, Ph.D.
Erika I. Boesen, Ph.D.
Corey R. Hopkins, Ph.D.
Neurotensin-receptor-1 (NTSR1) is regularly overexpressed in various cancers and contributes to the proliferation, survival, migration, invasion, and angiogenesis of tumors. NTSR1-targeting vectors have demonstrated promise in both diagnostic and therapeutic aspects. Unfortunately, the relatively poor in vivo metabolic stability and high renal uptake and retention of NTSR1-targeted compounds have hampered the translation to the clinic. In this research, we utilized a one-bead one-compound (OBOC) peptide library approach to make targeted modifications at the naturally charged residues of an NTS (4-13) sequence to discover an NTS derivative with comparable affinity to NTSR1, acceptable in vivo stability, and tolerable renal retention. Subsequent in vitro screening and analysis by LC-MS/MS and PEAKS® Studio software determined the modifications of interest for further investigation with the most favorable observed binding affinity toward NTSR1 were Gln at Glu4, Lys(Me2) at Lys6, and Arg(NO2) at Arg9.
Neeley, Trey, "Charge-Based Optimization of Neurotensin for Neurotensin-Receptor-1 Targeting Utilizing a One-Bead One-Compound Peptide Library Approach" (2019). Theses & Dissertations. 394.
Available for download on Sunday, August 15, 2021