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 these 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 availability, are associated with a dramatic loss of biological activity.