opioid, peptide, synthesis, addition
Medicinal-Pharmaceutical Chemistry | Organic Chemistry
In the United States, there is an ongoing opioid epidemic that has resulted in the increase of opioid-related deaths by 369% since 1999. Antagonists of the kappa opioid receptor (KOR) have shown potential in the treatment of addiction. The cyclic tetrapeptide JVA-4001, cyclo[Pro-Sar-Phe-D-Phe], antagonizes the KOR and agonizes the mu opioid receptor (MOR) in vivo. Its ability to antagonize the KOR suggests that it could be used to treat opioid addiction. The D-Trp4 residue of cyclo[Phe-D-Pro-Phe-D-Trp], a peptide with a similar scaffold to JVA-4001’s, was shown to be significant in the binding affinity to the KOR. In the present study, we report analogs that vary in the D-Phe4 position of JVA-4001 in hopes of gaining understanding of the structure-activity relationship of its scaffold. Fmoc solid-phase peptide synthesis was used to obtain the precursor linear peptides, which were analyzed using HPLC and MS. These methods confirmed that the linear peptides synthesized had purities of 97% and 92%. The linear precursors were cyclized from head-to-tail in dilute conditions. The cyclic peptides were purified using normal-phased chromatography, which was followed by flash chromatography.
Department 1 Awarding Honors Status
Hanson, C. (2019). Synthesis and Purification of Position 4 Analogs of the Opioid Peptide JVA-4001 (Undergraduate honors thesis, University of Redlands). Retrieved from https://inspire.redlands.edu/cas_honors/784
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