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

Moradi, Shayli Varasteh, Mansfeld, Friederike M. and Toth, Istvan (2013) Synthesis and in vitro evaluation of glycosyl derivatives of luteinizing hormone-releasing hormone (LHRH). Bioorganic and Medicinal Chemistry, 21 14: 4259-4265. doi:10.1016/j.bmc.2013.04.068


Author Moradi, Shayli Varasteh
Mansfeld, Friederike M.
Toth, Istvan
Title Synthesis and in vitro evaluation of glycosyl derivatives of luteinizing hormone-releasing hormone (LHRH)
Journal name Bioorganic and Medicinal Chemistry   Check publisher's open access policy
ISSN 0968-0896
1464-3391
Publication date 2013-07-15
Sub-type Article (original research)
DOI 10.1016/j.bmc.2013.04.068
Volume 21
Issue 14
Start page 4259
End page 4265
Total pages 7
Place of publication Kidlington, Oxford, United Kingdom
Publisher Pergamon
Collection year 2014
Language eng
Formatted 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.
Keyword Luteinizing hormone-releasing hormone
Carbohydrate moieties
Peptide modification
Permeability
Metabolic stability
Blood-brain-barrier
Epithelial Caco-2 cells
Phase peptide-synthesis
Solid-phase
Drug-delivery
Protein drugs
Oral delivery
Half-life
Acid
Endomorphin-1
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
School of Pharmacy Publications
 
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