Structural biochemistry XIII: Synthesis of luteinizing hormone-releasing hormone modification [Trp8]-LH-RH.

A fragment condensation method was utilized for synthesis of the Trp8-substituted luteinizing hormone-releasing hormone (LH-RH). tert-Butoxycarbonyl protection was employed for the alpha-amino positions, and benzyl protection was used for the phenol group of Tyr and the imidazole nitrogen of His. Peptide bond-forming reactions were performed using N-hydroxysuccinimide (for Trp), dicyclohexylcarbodiimide-1-hydroxybenzotriazole, 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide hydrochloride, or mixed carbonic anhydride methods. Biological evaluation of [Trp8]-LH-RH indicated no luteinizing hormone-releasing activity or inhibition of luteinizing hormone release over the dose ranges studied.