title: Synthesis and characterization of a new Peptide prodrug of glucosamine with enhanced gut permeability.
abstract: The aim of this study was to synthesize a peptide prodrug of glucosamine (GlcN) with increased gut permeability through the gut peptide transporter 1 (PepT1). Glycine-Valine ester derivative of GlcN (GVG) was synthesised using solid phase synthesis followed by characterization and evaluation of its physicochemical and intestinal stability. In addition, GVG was evaluated for its ability to be biotransformed to GlcN in the liver homogenate. In vitro absorption of the new prodrug through everted rat gut was also assessed. GVG demonstrated significant and meaningful increased gut permeability as compared with GlcN. It showed favorable stability in the gut and a quick cleavage to GlcN after exposure to the liver homogenate. In conclusion, a novel prodrug of glucosamine with superior gut permeability compared to GlcN was developed and successfully tested in vitro.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada; Department of Pharmaceutical Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, United States of America.
authors.forename: Hamed
authors.initials: H
authors.lastname: Gilzad Kohan
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada; Chapman University School of Pharmacy (CUSP), Harry and Diane Rinker Health Science Campus, Chapman University, Irvine, California, United States of America.
authors.forename: Kamaljit
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Fakhreddin
authors.initials: F
authors.lastname: Jamali
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001711:Biotransformation / Q000502:physiology; D004952:Esters / Q000737:chemistry; D005944:Glucosamine / Q000737:chemistry* / Q000378:metabolism*; D005998:Glycine / Q000737:chemistry; D007408:Intestinal Absorption / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008297:Male; D000074011:Peptide Transporter 1; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010539:Permeability; D011355:Prodrugs / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027981:Symporters / Q000378:metabolism; D014633:Valine / Q000737:chemistry
chemical_list: D004952:Esters; D000074011:Peptide Transporter 1; D010455:Peptides; D011355:Prodrugs; D027981:Symporters; D014633:Valine; D005944:Glucosamine; D005998:Glycine