Synthesis and biological activity of luteinizing hormone-releasing hormone and related peptides

Abstract

Syntheses of the decapeptide luteinizing hormone-releasing hormone, less thanGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2 are described. The basic properties of arginine can provide a simple repetitive isolation procedure for arginine-containing peptides. The biological activities of the decapeptide, of a range of fragments and modified fragments, and of two analogs with alteration in the series at position 4 were measured by in vitro incubation with sheep pituitary slices, measuring the liberated LH by bioassay. None of the compounds of shortened sequence were active, with the exception of less thanGlu-His-Trp which showed 1% of the decapeptide in one of four experiments. Neither [Ser(But)4]-LH-RH-nor [Leu4]-LH-RH showed significant activity indicating (despite the known activity of [Ala4]-LH-RH) the importance of this part of the structure for full biological activity.

PIP: Numerous syntheses of luteinizing homrone-releasing hormone (LH-RH), with a decapeptide structure of less than (Glu-His-Ser-Tyr-Gly-Leu-Arg-P ro-Gly-NH2, are described. Arginine offers a simple repetitive isolation procedure for arginine-containing peptides. In vitro incubation with sheep pituitary slices and measurement of liberated LH by bioassay were utilized to examine the biological activities of the de capeptide, of a range of fragments and modified fragments, and of 2 analogs with alteration in the serine at position 4. Except for less than Glu-His-Trp, which showed 1% of the activity of the decapeptide in 1 of 4 experiments, none of these compounds of shortened sequence showed activity. Despite the established activity of Ala4-LH-RH, neither Ser (But) 4-LH-RH or Leu4-LH-RH showed significant activity.