Analogs of Luteinizing Hormone-Releasing Hormone Containing Derivatives of Phenylalanine in Place of Tyrosine

The protected decapeptides pyroglutamyl-N ^im-benzylhistidyltryptophyl-O-benzylseryl-O-methyltyrosyl- glycylleucyl-N^G-tosylarginylprolylglycine amide and pyroglutamylhistidyltryptophyl-O-benzylseryl-p nitrophenylalanylglycylleucyl-N^G-tosylarginylprolylglycine amide were synthesized by solid-phase methods. They were converted to [5-(p-methoxyphenylalanine)]-LH-RH and [5-(p-nitrophenylalanine)]-LH-RH by reaction with sodium in liquid ammonia and anhydrous hydrogen fluoride, respectively Treatment of the p-nitrophenylalanine-protected peptide with sodium in liquid ammonia resulted in both the reduction of the nitro group to an amino group and the removal of the protecting groups to give [5-(p-aminophenylalanine)]-LH-RH in good yield. These analogs were assayed in vivo against pure natural LH-RH and found to possess the following LH-releasing activities: [5-(p-aminophenylalanine)]-LH-RH, 37%; [5-(p-methoxyphenylalanine)]-LH-RH, 24%; [5-(p-nitrophenylalanine)]-LH-RH, 5%.