Presentation Title

Progress Towards Synthesis of Analogs of the Opioid Peptide [D-Trp4]CJ-15,208

Faculty Mentor

Michael J Ferracane

Start Date

18-11-2017 10:00 AM

End Date

18-11-2017 11:00 AM

Location

BSC-Ursa Minor 111

Session

Poster 1

Type of Presentation

Poster

Subject Area

physical_mathematical_sciences

Abstract

The Commission on Combating Drug Addiction and the Opioid Crisis has estimated that opioids kill 142 Americans everyday, a number that is expected to continue growing. Compounds that antagonise the κ opioid receptor have demonstrated potential to treat drug addiction and other mood disorders. The cyclic peptide [D-Trp4]CJ-15,208 is a κ opioid antagonist, and its indole and phenyl groups have been shown to be important for this activity in vitro. However, this compound and related analogs behave as agonists in vivo. In this study, we report synthesis of several [D-Trp4]CJ-15,208 analogs—each varying in the identity of one amino acid residue—in order to better understand the unique activity of this molecular scaffold. Solid-phase peptide synthesis was utilised to obtain each analog’s linear precursor in yields up to 83% by HPLC; the identity and purity of each peptide was confirmed by MS and HPLC. The linear peptides are subsequently cyclised under dilute conditions, and (although this work is currently ongoing) preliminary results suggest up to 82% yield by HPLC.

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

Progress Towards Synthesis of Analogs of the Opioid Peptide [D-Trp4]CJ-15,208

BSC-Ursa Minor 111

The Commission on Combating Drug Addiction and the Opioid Crisis has estimated that opioids kill 142 Americans everyday, a number that is expected to continue growing. Compounds that antagonise the κ opioid receptor have demonstrated potential to treat drug addiction and other mood disorders. The cyclic peptide [D-Trp4]CJ-15,208 is a κ opioid antagonist, and its indole and phenyl groups have been shown to be important for this activity in vitro. However, this compound and related analogs behave as agonists in vivo. In this study, we report synthesis of several [D-Trp4]CJ-15,208 analogs—each varying in the identity of one amino acid residue—in order to better understand the unique activity of this molecular scaffold. Solid-phase peptide synthesis was utilised to obtain each analog’s linear precursor in yields up to 83% by HPLC; the identity and purity of each peptide was confirmed by MS and HPLC. The linear peptides are subsequently cyclised under dilute conditions, and (although this work is currently ongoing) preliminary results suggest up to 82% yield by HPLC.