SYNTHESIS AND BIOLOGICAL ACTIVITY OF POSITION 1 ANALOGS OF LH‐RH

Abstract

(Formyl-sarcosine)1-LH-RH [luteinizing hormone releasing hormone] (I), (acetyl-sarcosine)1-LH-RH (II), (2-pyrrolidone-4-carboxylic acid)1-LH-RH (III), (N-methyl-2-pyrrolidone-4-carboxylic acid)1-LH-RH (IV, hydroxyproline1-LH-RH (V) and (cyclopentane-carboxylic acid)1-LH-RH (VI) were synthesized by solid phase methods on a benzhydrylamine resin support. Peptides I-IV were assayed for LH- and FSH[follicle stimulating hormone]-releasing activity over a 4 h period after s.c. injection into immature male rats in order to detect any prolongation of activity. The peptides had the following integrated LH-releasing activities compared with LH-RH: I, 64%; II, 72%; III, 19%; IV, 58%. None of the peptides were longer acting than LH-RH. Peptides V and VI were far less active, 0.001 and 1.4%, respectively.