Tryptophan reduction and histidine racemization during deprotection by catalytic transfer hydrogenation of an analog of the luteinizing hormone releasing factor.
(D-Trp)6-LHRH:pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-GlyNH2 was prepared by solid-phase peptide synthesis using the nitro group to protect the guanidine side chain of the arginyl residue. Removal of the side-chain protecting groups was carried out by catalytic transfer hydrogenation (CTH) using palladium acetate/ammonium formate or palladium on charcoal/formic acid. We show in this paper that this deprotection method induces i) reduction of the tryptophan residue and ii) epimerization at the histidine level (with palladium acetate/ammonium formate). Despite the formation of significant amounts of reduced peptide, CTH enabled us to obtain (D-Trp)6-LHRH in relatively good yield.
Méry
J
J
Centre for Macromolecular Biochemistry Research, National Institute of Health and Medical Research, Montpellier, France.
Calas
B
B
D002851:Chromatography, High Pressure Liquid; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D006639:Histidine; D007202:Indicators and Reagents; D009904:Optical Rotation; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D017329:Triptorelin Pamoate; D014364:Tryptophan
D007202:Indicators and Reagents; D017329:Triptorelin Pamoate; D007987:Gonadotropin-Releasing Hormone; D006639:Histidine; D014364:Tryptophan