Repetitive BOP coupling (REBOP) in solid phase peptide synthesis. Luliberin synthesis as model.
The coupling reagent (benzotriazol-1-yloxy)tris-(dimethylamino)phosphonium (BOP) hexafluorophosphate was tested in the synthesis of luliberin (LH-RH) with inexpensive classically protected Boc-amino acids, in slight excess, and benzhydryl amino resin, without any other additive. The good solubility of this reagent and its by-products is of particular interest for automated peptide synthesis. [D-His2]LH-RH was also synthesized and compared with LH-RH by proton nuclear magnetic resonance spectroscopy. As shown by the biological tests and the high performance liquid chromatography study, unprotected pyroGlu and Boc-His can be used without any significant racemization but Boc-His(Boc) was found to be preferable since it gave no detectable racemization and no by-products. The difficult isolation of the minority D-derivative from the crude preparation of LH-RH was resolved by a recycling procedure in reversed phase HPLC.
Seyer
R
R
CNRS-INSERM, Center of Pharmacology-Endocrinology, Montpellier, France.
Aumelas
A
A
Caraty
A
A
Rivaille
P
P
Castro
B
B
D000595:Amino Acid Sequence; D007987:Gonadotropin-Releasing Hormone / Q000138:chemical synthesis* / Q000302:isolation & purification; D007202:Indicators and Reagents; D008969:Molecular Sequence Data; D009943:Organophosphorus Compounds; D010455:Peptides / Q000138:chemical synthesis*; D013237:Stereoisomerism
D007202:Indicators and Reagents; D009943:Organophosphorus Compounds; D010455:Peptides; D007987:Gonadotropin-Releasing Hormone; C031032:benzotriazol-1-yloxy-tris(dimethylamino)phosphonium