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.

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Nov 18th, 10:00 AM Nov 18th, 11:00 AM

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.