Date of Award

2019

Document Type

Dissertation/Thesis

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Cudic, Predrag

Abstract

Pain management with opioid drugs is difficult due to the risk of side effects such as respiratory depression, constipation, and addiction. Given these issues, there is an urgent need for safe painkillers. The cyclic peptide odorranalectin can bypass the blood-brain barrier (BBB) after intranasal delivery. Grafting peptide-based opioid receptor agonists onto the OL scaffold delivered the CNS-active peptides to the brain. Our group discovered a lead peptide with analgesic activity in acute and chronic pain models in mice. The peptide showed affinity towards kappa (KOR) and delta opioid receptors. Agonistic activation of KOR leads to potent analgesic effects without high potential for abuse and inhibits dopamine and serotonin release. Integration of 5-hydroxytryptophan and L-3,4-dihydroxyphenylalanine, precursors to serotonin and dopamine, into the lead peptide may reduce KOR activation side effects. KOR agonists containing 5-hydroxytryptophan and L-3,4-dihydroxyphenylalanine were synthesized. Preliminary results in mice indicated improved analgesic effect compared to the parent peptide.

Comments

Includes bibliography.

Extent

35 p.

Identifier

FAUHT00093

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