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.

Structural Biochemistry XIII: Synthesis of Luteinizing Hormone - Releasing Hormone Modification [ Trp8]- LH - RH

“…This discovery has impressive potential for solving certain medical problems, from overcoming a cause of female sterility to opening new approaches to contraception. Therefore, synthetic efforts directed a t the decapeptide hormone and related substances have been undertaken and presently underlie the major effort in decapeptide chemistry (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). BACKGROUND One facet of the LH-RH potential that seemed particularly attractive was that a suitable modification of this hormone might inhibit certain cancer types, e.g., of the ovary.…”