UC Irvine

Three analogues of LH-RH in which Dextrarotatory amino acids were substituted for the Gly6, and two additional analogues in which the Leu7 residue was also modified, were subjected to enzymic preparations derived from rat hypothalamus or anterior pituitary. These enzymes, known to cleave LH-RH, preferentially at the Gly6-Leu7 position, proved less effective in degrading all the analogues tested. Among the Gly6 substituted analogues, [D-Trp6] LH-RH, having the highest LH-releasing activity, was most resistant to degradation. Additional modification, at position 7, although rendering the analogues immune to enzymic attack, did not further enhance their biological potency. These data suggest that degradation of LH-RH is a physiological determinant of its biological activity and has therefore to be considered with on designing new, potent analogues of the hormone.