Glycopeptide drugs: A pharmacological dimension between "Small Molecules" and "Biologics".

Peptides
Christopher R ApostolRobin Polt

Abstract

Peptides are an important class of molecules with diverse biological activities. Many endogenous peptides, especially neuropeptides and peptide hormones, play critical roles in development and regulating homeostasis. Furthermore, as drug candidates their high receptor selectivity and potent binding leads to reduced off-target interactions and potential negative side effects. However, the therapeutic potential of peptides is severely hampered by their poor stability in vivo and low permeability across biological membranes. Several strategies have been successfully employed over the decades to address these concerns, and one of the most promising strategies is glycosylation. It has been demonstrated in numerous cases that glycosylation is an effective synthetic approach to improve the pharmacokinetic profiles and membrane permeability of peptides. The effects of glycosylation on peptide stability and peptide-membrane interactions in the context of blood-brain barrier penetration will be explored. Numerous examples of glycosylated analogues of endogenous peptides targeting class A and B G-protein coupled receptors (GPCRs) with an emphasis on O-linked glycopeptides will be reviewed. Notable examples of N-, S-, and C-linked glycopep...Continue Reading

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Citations

Dec 23, 2020·Chemistry & Biodiversity·Karol Wtorek, Anna Janecka
Jul 21, 2021·Cell Chemical Biology·Daisuke FujinamiWilfred A van der Donk
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christopher R ApostolRobin Polt

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