Dynorphin 1-17 biotransformation peptides: properties, challenges and solutions for future therapeutics development

It is well established that endogenously produced dynorphin 1-17 (DYN 1-17) is susceptible to enzymatic degradation, producing a variety of unique fragments in different tissue matrices and disease pathologies. DYN 1-17 and its major biotransformation fragments have significant roles in neurological and inflammatory disorders upon interacting with opioid and non-opioid receptors at both central and peripheral levels, thus highlighting their potential as drug candidates. Nevertheless, their development as promising therapeutics is challenged by several issues. This review aims to provide the latest and comprehensive updates on DYN 1-17 biotransformed peptides, including their pharmacological roles, pharmacokinetic studies and relevant clinical trials. Challenges in their development as potential therapeutics and proposed solutions to overcome these limitations are also discussed. This is a summary of published articles on the important roles of dynorphin 1-17 and its fragments in several disease pathologies, including neurological and inflammatory disorders. Dynorphin 1-17, which consists of 17 amino acids, is a substance produced in the human body that is easily degraded by the body's enzymes, producing a shorter chain of amino acids. For the past few decades, researchers have attempted to utilize these substances to treat the above-mentioned conditions. However, upon introduction, these substances are rapidly degraded by the enzymes, which hinder the molecules from reaching the site of action. Therefore, many studies have focused on addressing the degradation issue in order to benefit from the important role of dynorphin 1-17 and its fragments in treating respective diseases. Previous researchers have attempted structural modification of these substances by either changing the terminals of the amino acid chains or attaching them to other agents to increase the resistance of dynorphin 1-17 and its fragments toward enzymatic breakage. These substances were also incorporated into nano-sized delivery systems, which have been shown to protect the molecules while improving their delivery to different parts of the body. These results showed that the structurally modified dynorphin 1-17 and its fragments and their nano-sized delivery system could improve the stability of the molecules and allow them to be used to treat many conditions.