On the role of tryptophan in luteinizing-hormone-releasing hormone (luliberin).

The tryptophan residue of luteinizing-hormone-releasing hormone (luliberin) was chemically modified to produce the following analogs: [Trp(o)3]luliberin, Trp-(2,4-dinitrophenylsulfenyl)-luliberin, Trp-(2-hydroxy-5-nitrobenzyl)luliberin, (Trp-S-luliberin)2, Trp-CH3S-luliberin and Trp-formyl-luliberin. The luteinizing-hormone-releasing activity of those analogs was determined by bioassay in vitro and found to be 0.2%, 0.2%, 0.6%, 1.5%, 1.7% and 7% of that of the natural hormone, respectively. These results demonstrate that alterations in the indole moiety of tryptophan-3, which lead to a reduction in its electron density or sterically restrict its electron avaliability, are associated with a dramatic loss of biological activity.