Synthesis and In Vitro Characterization of Glycopeptide Drug Candidates Related to PACAP1–23 |
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| Authors: | Christopher R. Apostol,Parthasaradhireddy Tanguturi,Lajos Z. Szabò ,Daniel Varela,Thiago Gilmartin,John M. Streicher,Robin Polt |
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| Affiliation: | 1.Department of Chemistry and Biochemistry, BIO5, The University of Arizona, 1306 E. University Blvd, Tucson, AZ 85721, USA; (C.R.A.); (L.Z.S.);2.Department of Pharmacology, College of Medicine, The University of Arizona, 1501 N. Campbell Ave, Tucson, AZ 85724, USA; (P.T.); (J.M.S.);3.Facultat de Quìmica Tarragona, Universitat Rovera I Virgili, 43007 Barcelona, Spain; (D.V.); (T.G.) |
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| Abstract: | The search for efficacious treatment of neurodegenerative and progressive neuroinflammatory diseases continues, as current therapies are unable to halt or reverse disease progression. PACAP represents one potential therapeutic that provides neuroprotection effects on neurons, and also modulates inflammatory responses and circulation within the brain. However, PACAP is a relatively long peptide hormone that is not trivial to synthesize. Based on previous observations that the shortened isoform PACAP1–23 is capable of inducing neuroprotection in vitro, we were inspired to synthesize shortened glycopeptide analogues of PACAP1–23. Herein, we report the synthesis and in vitro characterization of glycosylated PACAP1–23 analogues that interact strongly with the PAC1 and VPAC1 receptors, while showing reduced activity at the VPAC2 receptor. |
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| Keywords: | glycosylation, glycopeptide, stroke, Alzheimer’ s, Parkinson’ s |
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