title: The stability of lipidic analogues of GnRH in plasma and kidney preparations: the stereoselective release of the parent peptide.
abstract: The conjugation of a lipoamino acid to the N-terminus of Gonadotropin releasing hormone (GnRH) produces a lipophilic peptide from which the parent GnRH peptide is released into solution on treatment with plasma and kidney enzyme preparation. Our findings show that one stereoisomer of the Laa is cleaved very rapidly, providing a bolus dose of the peptide while the opposite stereoisomer is cleaved much more slowly, providing prolonged elevation of peptide concentration. The Laa-Glu linkage appears to act as a two phase prodrug system.
authors.affiliation: School of Molecular and Microbial Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia. j.blanchfield@uq.edu.au
authors.forename: Joanne T
authors.initials: JT
authors.lastname: Blanchfield
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Lew
authors.forename: A Ian
authors.initials: AI
authors.lastname: Smith
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004355:Drug Stability; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D010949:Plasma / Q000378:metabolism; D011355:Prodrugs; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D011355:Prodrugs; D007987:Gonadotropin-Releasing Hormone