title: Synthesis and in vitro evaluation of glycosyl derivatives of luteinizing hormone-releasing hormone (LHRH).
abstract: Luteinizing hormone-releasing hormone (LHRH) analogues are used extensively for the treatment of various hormone-dependent diseases. However, none of the currently marketed derivatives can be administered orally. Modification of peptide sequences by attachment of carbohydrate moieties is a promising strategy that may increase the metabolic stability of the target peptide and enhance its transport across cell membranes, subsequently improving peptide bioavailability. In this study, either the N- or C-terminus of the LHRH peptide was altered by attachment of carbohydrate moieties. Caco-2 cells were chosen as an in vitro model to investigate both the permeability and stability of the new LHRH analogues. Our findings show that conjugating sugar moieties to the N-terminus of the LHRH peptide significantly increased both permeability and metabolic stability of most of the modified LHRH derivatives.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Shayli Varasteh
authors.initials: SV
authors.lastname: Moradi
authors.forename: Friederike M
authors.initials: FM
authors.lastname: Mansfeld
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D004355:Drug Stability; D006031:Glycosylation; D007987:Gonadotropin-Releasing Hormone / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D054852:Small Molecule Libraries; D007987:Gonadotropin-Releasing Hormone