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Lee YS text re-revision-final.pdf
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Final Accepted Manuscript
Affiliation
University of Arizona, Department of Chemistry and BiochemistryIssue Date
2016Keywords
reviewOpioid
Cyclic peptides
polycyclic
opioid receptors
analgesia
central nervous system
blood brain barrier penetration
bioavailability
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Show full item recordPublisher
BENTHAM SCIENCE PUBL LTDCitation
Cyclic Opioid Peptides. 2016, 23 (13):1288-303 Curr. Med. Chem.Journal
Current medicinal chemistryRights
Copyright © 2016, Eureka Science Ltd.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
For decades the opioid receptors have been an attractive therapeutic target for the treatment of pain. Since the first discovery of enkephalin, approximately a dozen endogenous opioid peptides have been known to produce opioid activity and analgesia, but their therapeutics have been limited mainly due to low blood brain barrier penetration and poor resistance to proteolytic degradation. One versatile approach to overcome these drawbacks is the cyclization of linear peptides to cyclic peptides with constrained topographical structure. Compared to their linear parents, cyclic analogs exhibit better metabolic stability, lower offtarget toxicity, and improved bioavailability. Extensive structure-activity relationship studies have uncovered promising compounds for the treatment of pain as well as further elucidate structural elements required for selective opioid receptor activity. The benefits that come with employing cyclization can be further enhanced through the generation of polycyclic derivatives. Opioid ligands generally have a short peptide chain and thus the realm of polycyclic peptides has yet to be explored. In this review, a brief history of designing ligands for the opioid receptors, including classic linear and cyclic ligands, is discussed along with recent approaches and successes of cyclic peptide ligands for the receptors. Various scaffolds and approaches to improve bioavailability are elaborated and concluded with a discourse towards polycyclic peptides.Note
12 month embargo. Published 1 April 2016.ISSN
1875-533XPubMed ID
27117332Version
Final accepted manuscriptae974a485f413a2113503eed53cd6c53
10.2174/0929867323666160427123005
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