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Development of a Backbone Cyclic Peptide Library as Potential Antiparasitic Therapeutics Using Microwave Irradiation
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Backbone modification of a polypeptide drug alters duration of action in vivo
Ross W Cheloha1, Akira Maeda2, Thomas Dean2
1Department of Chemistry, University of Wisconsin, Madison, Wisconsin, USA.
Abstract:
Systematic modification of the backbone of bioactive polypeptides through β-amino acid residue incorporation could provide a strategy for generating molecules with improved drug properties, but such alterations can result in lower receptor affinity and potency. Using an agonist of parathyroid hormone receptor-1 (PTHR1), a G protein-coupled receptor in the B-family, we present an approach for α→β residue replacement that enables both high activity and improved pharmacokinetic properties in vivo.
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