Plant peptide hormone phytosulfokine (PSK-alpha): synthesis of new analogues and their biological evaluation.

Phytosulfokine-alpha (PSK-alpha), a sulfated growth factor (H-Tyr(SO3H)-Ile-Tyr(SO3H)-Thr-Gln-OH) universally found in both monocotyledons and dicotyledons, strongly promotes proliferation of plant cells in culture. In our studies on structure/activity relationship in PSK-alpha the synthesis of a series of analogues was performed: H-D-Tyr(SO3H)1]- (9), H-Phe(4-SO3H)1]- (10), H-D-Phe(4-SO3H)1]- (11), H-Phg(4-SO3H)1]- (12), H-D-Phg(4-SO3H)1]- (13), H-Phe(4-NHSO2CH3)1]- (14), H-D-Phe(4-NHSO2CH3)1]- (15), H-Phe(4-NO2)1]- (16), H-D-Phe(4-NO2)1]- (17), H-Phg(4-NO2)1]- (18), H-D-Phg(4-NO2)1]- (19), H-Hph(4-NO2)1]- (20), H-Phg(4-OSO3H)1]- (21), Phe(4-NO2)3]- (22), Phg(4-NO2)3]- (23), Hph(4-NO2)3]- (24), H-Phe(4-SO3H)1, Phe(4-SO3H)3]- (25) H-Phe(4-NO2)1, Phe(4-NO2)3]- (26), H-Phg(4-NO2)1, Phg(4-NO2)3]- (27), H-Hph(4-NO2)1, Hph(4-NO2)3]- (28) and Val3]- PSK-alpha (29). For modification of the PSK-alpha peptide chain the novel amino acids and their derivatives were synthesized, such as: H-L-Phg(4-SO3H)-OH (1), H-D-Phg(4-SO3H)-OH (2), Fmoc-Phg(4-SO3H)-OH (3), Fmoc-D-Phg(4-SO3H)-OH (4), Boc-Phg(4-NHSO2CH3)-OH (5), Boc-D-Phg(4-NHSO2CH3)-OH (6) Boc-Phe(4-NHSO2CH3)-OH (7), and Boc-D-Phe(4-NHSO2CH3)-OH (8). Peptides were synthesized by a solid phase method according to the Fmoc procedure on a Wang-resin. Free peptides were released from the resin by 95% TFA in the presence of EDT. All peptides were tested by competitive binding assay to the carrot membrane using 3H-labelled PSK according to the Matsubayashi et al. test.