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 two different deblocking procedures which used hydrogen chloride in formic acid and hydrogen chloride in acetic acid containing 1% 2‐mercaptoethanol. After some fundamental studies on the former reagent with respect to deblocking efficiency toward the Boc group, 0.5 M hydrogen chloride (a 10‐fold molar excess with respect to the N‐terminal Boc group) in formic acid was used in the present synthesis. The two synthetic products exhibited the same chemical and biological properties as an authentic LH‐RH. Hydrogen chloride 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 hydrogen chloride in acetic acid. A derivative of the synthetic LH‐RH formylated at the indole nitrogen had a greatly diminshed biological activity, indicating that the intact indole side chain is essential for the activity.