The stability of lipidic analogues of GnRH in plasma and kidney preparations: the stereoselective release of the parent peptide.
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.
Blanchfield
Joanne T
JT
School of Molecular and Microbial Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia. j.blanchfield@uq.edu.au
Lew
Rebecca A
RA
Smith
A Ian
AI
Toth
Istvan
I
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
D011355:Prodrugs; D007987:Gonadotropin-Releasing Hormone