SOLID PHASE SYNTHESIS OF PORCINE LH-RELEASING HORMONE WITH HYDROGEN CHLORIDE IN FORMIC ACID AS THE DEBLOCKING REAGENT*

Abstract

The decapeptide corresponding to the amino acid sequence of porcine luteinizing hormone-releasing hormone (LH-RH) which involves 1 mol of tryptophan was synthesized via solid phase synthesis with 2 different deblocking procedures which used HCl in formic acid and HCl in acetic acid containing 1% 2-mercaptoethanol. After some fundamental studies on the former reagent with respect to deblocking efficiency toward the Boc [tert-butyloxycarbonyl] group, 0.5 M HCl (a 10-fold molar excess with respect to the N-terminal Boc group) in formic acid was used in the present synthesis. The 2 synthetic products exhibited the same chemical and biological properties as an authentic LH-RH. HCl in formic acid has proved effective without a scavenger although loss of peptide from the resin occurred to a somewhat greater extent than that with HCl in acetic acid. A derivative of the synthetic LH-RH formylated at the indole N had a greatly diminished biological activity, indicating that the intact indole side chain is essential for the activity.