Presentation Title
Progress Towards the Synthesis of Opioid Peptide [D-Trp4]CJ-15,208 Analogs
Faculty Mentor
Michael Ferracane
Start Date
18-11-2017 10:00 AM
End Date
18-11-2017 11:00 AM
Location
BSC-Ursa Minor 117
Session
Poster 1
Type of Presentation
Poster
Subject Area
physical_mathematical_sciences
Abstract
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 have shown potential in the treatment of addiction (J. Nat. Prod. 2013, 76, 433). The cyclic peptide [D-Trp4]CJ-15,208 is a kappa opioid receptor antagonist in vitro but behaves as an agonist in vivo. The D-Trp4 residue of this peptide was shown to be significant for the molecule’s affinity for the kappa opioid receptor. In the present study, we report analogs that vary in the D-Trp4 position of this cyclic peptide in hopes of finding an analog that retains antagonist behavior in vivo. 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 were synthesized with purities of 49% and 58% by HPLC. The subsequent cyclization, performed under dilute conditions, is currently ongoing.
Progress Towards the Synthesis of Opioid Peptide [D-Trp4]CJ-15,208 Analogs
BSC-Ursa Minor 117
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 have shown potential in the treatment of addiction (J. Nat. Prod. 2013, 76, 433). The cyclic peptide [D-Trp4]CJ-15,208 is a kappa opioid receptor antagonist in vitro but behaves as an agonist in vivo. The D-Trp4 residue of this peptide was shown to be significant for the molecule’s affinity for the kappa opioid receptor. In the present study, we report analogs that vary in the D-Trp4 position of this cyclic peptide in hopes of finding an analog that retains antagonist behavior in vivo. 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 were synthesized with purities of 49% and 58% by HPLC. The subsequent cyclization, performed under dilute conditions, is currently ongoing.