Synthesis and in vitro evaluation of glycosyl derivatives of luteinizing hormone-releasing hormone (LHRH)

Shayli Varasteh Moradi, Friederike M. Mansfeld, Istvan Toth

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4259-4265
Number of pages7
JournalBioorganic & Medicinal Chemistry
Volume21
Issue number14
DOIs
Publication statusPublished - 15 Jul 2013
Externally publishedYes

Keywords

  • Carbohydrate moieties
  • Luteinizing hormone-releasing hormone
  • Metabolic stability
  • Peptide modification
  • Permeability

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