Lipophilic Peptides: Synthesis of Lauroyl Thyrotropin-Releasing Hormone and Its Biological Activity

Abstract
Thyrotropin-releasing hormone (TRH) was derivatized by chemical attachment of lauric acid to the N-terminal pyroglutamyl group. The product was confirmed to be more lipophilic than TRH by high-performance liquid chromatography and measurement of partition coefficients. The central nervous system activity and endocrine activity of the lauroyl derivative were only slightly reduced, to 81 and 64% of the parent TRH, respectively. Lipophilic derivatization may be generally applicable to transmembrane delivery of peptides.