1.Applications of BOP reagent in solid phase synthesis. Advantages of BOP reagent for difficult couplings exemplified by a synthesis of [Ala 15]-GRF(1-29)-NH2.
Fournier A1, Wang CT, Felix AM. Int J Pept Protein Res. 1988 Jan;31(1):86-97.
The BOP reagent [benzotriazol-l-yl-oxy-tris-(dimethylamino)phosphonium hexa-fluorophosphate] introduced by Castro et al. [Tetrahedron Lett. (1975) 14, 1219-1222] is ideally suited for solid phase peptide synthesis. The rate of coupling using BOP compared favorably to DCC and other methods of activation including the symmetrical anhydride and DCC/HOBt procedures. BOP couplings using the solid phase procedure proceeded more rapidly and to a greater degree of completion for peptide bond formations that were previously determined to be very slow using the conventional DCC method. Stepwise solid phase peptide synthesis using BOP was successfully utilized for the preparation of the (22-29) and (13-29) fragments of [Ala15]-GRF(1-29)-NH2. Single couplings with 3 equiv. BOP and Boc-amino acids and 5.3 equiv. of diisopropylethylamine in DMF were used for each cycle. The yields of the fragments were superior and the purities comparable using the BOP procedure (single couplings) to those observed using multiple couplings via the DCC coupling method.
2.Plant peptide hormone phytosulfokine (PSK-alpha): synthesis of new analogues and their biological evaluation.
Bahyrycz A1, Matsubayashi Y, Ogawa M, Sakagami Y, Konopińska D. J Pept Sci. 2004 Jul;10(7):462-9.
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).
3.A recombinant human stromelysin catalytic domain identifying tryptophan derivatives as human stromelysin inhibitors.
Ye QZ1, Johnson LL, Nordan I, Hupe D, Hupe L. J Med Chem. 1994 Jan 7;37(1):206-9.
The human stromelysin catalytic domain (SCD) has been expressed in Escherichia coli and purified to homogeneity (Ye et al. Biochemistry 1992, 31, 11231). We have used this recombinant SCD for inhibitor screening and identified tryptophan derivatives as competitive inhibitors of SCD. Both Cbz-L-Trp-OH (1, IC50 2.5 microM, Ki 2.1 microM) and Boc-L-Trp-OH (3, IC50 10 microM, Ki 8 microM) showed good inhibitory activity. Modification at the indole nitrogen with formyl or mesitylene-2-sulfonyl group (16, IC50 34 microM, Ki 28 microM; 17, IC50 63 microM, Ki 52 microM) showed reduced activity. The amide Cbz-L-Trp-NH2 (13) was not active, but esters Cbz-L-Trp-OSu (14, IC50 13 microM, Ki 11 microM) and Boc-L-Trp-OSu (15, IC50 102 microM, Ki 84 microM) showed activity. Aromatic amino acid derivatives Cbz-L-Tyr-OH (18, IC50 24 microM, Ki 20 microM) and Cbz-L-Phe-OH (26, IC50 40 microM, Ki 33 microM) were also active, but other amino acid derivatives had no activity.
