New proctolin analogues modified by the novel D-or L-phenylglycine derivatives. Synthesis and biological studies

New analogues of insect neuromodulator proctolin (H-Arg-Tyr-Leu-Pro-Thr-OH), modified in position 2 of the peptide chain by L-or D-phenylglycine and its 4-substituted derivatives were synthesized. For modification of proctolin a series of novel L-or D-phenylglycine derivatives H-Phg(4-NO₂)-OH (1), Boc-Phg(4-NO₂)-OH (2), Boc-Phg(4-Me₂N)-OH (3), H-Phg(4-OBzl)-OH (4), Boc-Phg(4-OBzl)-OH (5), H-D-Phg(4-NO₂)-OH (6), Boc-D-Phg(4-NO₂,)-OH (7), Boc-D-Phg(4-Me₂N)-OH (8), were used. The following proctolin analogues were synthesized: H-Arg-Phg-Leu-Pro-Thr-OH (9), H-Arg-D-Phg-Leu-Pro-Thr-OH (10), H-Arg-Phg(4-OH)-Leu-Pro-Thr-OH (11), H-Arg-D-Phg(4-OH)-Leu-Pro-Thr-OH (12), H-Arg-Phg(4-NO₂)-Leu-Pro-Thr-OH (13), H-Arg-D-Phg(4-NO₂)-Leu-Pro-Thr-OH (14), H-Arg-Phg(4-NH₂)-Leu-Pro-Thr-OH (15), H-Arg-D-Phg(4-NH₂)-Leu-Pro-Thr-OH (16), H-Arg-Phg(4-NMe₂)-Leu-Pro-Thr-OH (17), H-Arg-D-Phg(4-NMe₂)-Leu-Pro-Thr-OH (18). Myotropic activity of proctolin analogues 9-18 was assayed in vitro on the semi-isolated heart of the mealworm Tenebrio molitor and on the foregut of the locust Schistocerca gregaria. All analogues showed a weak or none activity.