Abstract: Based on a new concept of protease-resistant long acting peptides design, the functional groups with proton-donors and proton-acceptors were introduced to the N-terminal and position 6 of LHRH antagonist, and a series of novel LHRH antagonist analogues were synthesized. The bioactivity of them was evaluated in rats by a testosterone test model. The designed peptides showed a longer duration of inhibiting testosterone secretion than the parent peptide and control. Peptide 1e inhibited the testosterone secretion for 48 h in intact rats(Cetrorelix: 8 h). The experimental results not only support the proposed concept of the long acting peptide design, but also supply some new candidate compounds for the development of long acting LHRH antagonist drugs.

Key words: LHRH antagonist, Long acting peptide, Testosterone