{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:27:16Z","timestamp":1780471636587,"version":"3.54.1"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["No number"],"award-info":[{"award-number":["No number"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R43DA026653 and R44 DA026653"],"award-info":[{"award-number":["R43DA026653 and R44 DA026653"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In previous work we evaluated an opioid glycopeptide with mixed \u03bc\/\u03b4-opioid receptor agonism that was a congener of leu-enkephalin, MMP-2200. The glycopeptide analogue showed penetration of the blood\u2013brain barrier (BBB) after systemic administration to rats, as well as profound central effects in models of Parkinson\u2019s disease (PD) and levodopa (L-DOPA)-induced dyskinesia (LID). In the present study, we tested the glycopeptide BBI-11008 with selective \u03b4-opioid receptor agonism, an analogue of deltorphin, a peptide secreted from the skin of frogs (genus Phyllomedusa). We tested BBI-11008 for BBB-penetration after intraperitoneal (i.p.) injection and evaluated effects in LID rats. BBI-11008 (10 mg\/kg) demonstrated good CNS-penetrance as shown by microdialysis and mass spectrometric analysis, with peak concentration levels of 150 pM in the striatum. While BBI-11008 at both 10 and 20 mg\/kg produced no effect on levodopa-induced limb, axial and oral (LAO) abnormal involuntary movements (AIMs), it reduced the levodopa-induced locomotor AIMs by 50% after systemic injection. The N-methyl-D-aspartate receptor antagonist MK-801 reduced levodopa-induced LAO AIMs, but worsened PD symptoms in this model. Co-administration of MMP-2200 had been shown prior to block the MK-801-induced pro-Parkinsonian activity. Interestingly, BBI-11008 was not able to block the pro-Parkinsonian effect of MK-801 in the LID model, further indicating that a balance of mu- and delta-opioid agonism is required for this modulation. In summary, this study illustrates another example of meaningful BBB-penetration of a glycopeptide analogue of a peptide to achieve a central behavioral effect, providing additional evidence for the glycosylation technique as a method to harness therapeutic potential of peptides.<\/jats:p>","DOI":"10.3390\/ijms22010020","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T20:39:29Z","timestamp":1608669569000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Delta-Specific Opioid Glycopeptide BBI-11008: CNS Penetration and Behavioral Analysis in a Preclinical Model of Levodopa-Induced Dyskinesia"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8280-5299","authenticated-orcid":false,"given":"Mitchell J.","family":"Bartlett","sequence":"first","affiliation":[{"name":"Department of Neurology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar S.","family":"Mabrouk","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lajos","family":"Szab\u00f2","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Flores","sequence":"additional","affiliation":[{"name":"Graduate Interdisciplinary Program in Physiological Sciences, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate L.","family":"Parent","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4305-5111","authenticated-orcid":false,"given":"Jean M.","family":"Bidlack","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Heien","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert T.","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Polt","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry, University of Arizona, Tucson, AZ 85721, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4999-3309","authenticated-orcid":false,"given":"Torsten","family":"Falk","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Graduate Interdisciplinary Program in Physiological Sciences, University of Arizona, Tucson, AZ 85724, USA"},{"name":"Department of Pharmacology, University of Arizona, Tucson, AZ 85724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Olanow, W.C., Stocchi, F., and Lang, A.E. 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