Tripeptides with non-code amino acids as potential serine proteases inhibitors

Figures & data

Table 1.  Structure of obtained peptides: H-D-Ser-AA-Arg-OH.

Compound	AA
1	Phenylglycine	Phg
2	Phenylalanine	Pha
3	Homophenylalanine	homoPhe
4	Cyclohexylglycine	Chg
5	Cyclohexylalanine	Cha
6	Homocyclohexylalanine	homoCha
7	α-methylphenylalanine	α-MePhe
8	1-Aminocyclohexyl carboxylic acid	1-ACH

Table 2.  Analytical data of the synthesized compounds.

No	Yield [%]	Retention time [min.]	MW	[M+H]^+
1	57	12.87	408.4	409.6
2	46	11.97	394.4	395.5
3	51	10.46	422.5	423.4
4	52	13.56	414.5	415.7
5	49	14.48	400.5	401.3
6	50	15.33	428.5	429.6
7	48	11.67	422.5	423.7
8	49	12.51	386.5	387.4

Table 3.  Inhibition of H-D-Ser-AA-Arg-OH on the amidolytic activity of enzymes.

No	AA	Ki [µM]
		Urokinase S-2444	Thrombin S-2238	Trypsin Bzl-L-Arg-pNA HCl	Plasmin S-2251
1	Phg	487.8 ± 39.0	22.9 ± 1.8	26.3 ± 1.9	5.7 ± 0.5
2	Phe	544 ± 43.5	12.1 ± 0.9	22.9 ± 1.7	8.7 ± 0.7
3	homoPhe	565.8 ± 43.9	16.1 ± 1.3	23.9 ± 1.8	5.9 ± 0.5
4	Chg	321.9 ± 26.8	5.02 ± 0.4	48.4 ± 3.7	7.7 ± 0.7
5	Cha	246.97 ± 19.7	19.8 ± 1.6	30.9 ± 2.5	8.9 ± 0.7
6	homoCha	451.2 ± 36.6	18.1 ± 1.4	27.2 ± 1.9	11.2 ± 0.9
7	αMePhe	275.6 ± 21.9	12.47 ± 0.9	28.2 ± 2.2	7.9 ± 0.7
8	1ACH	395.1 ± 31.7	14.99 ± 1.2	26.2 ± 1.8	7.7 ± 0.7
	Ac-Leu-Leu-Arg-H	–	–	8 ± 0.7 nM	8.2 ± 0.7 nM
	Ac-Leu-Leu-Arg-COCHO	–	–	1.9 µM^Citation27	4.9 µM^Citation27

Table 4.  The nonviability of MDA cells treated for 24 h with different concentrations of the synthesized peptides.

Compounds	IC50 [μM] (% of control ± 2)a
1	306
2	283
3	272
4	245
5	263
6	270
7	278
8	258
Ac-Leu-Leu-Arg-H	580

^a Mean values ± SD from three independent experiments done in duplicate.

Enomoto R, Sugahara C, Komai T, Suzuki C, Kinoshita N, Hosoda A et al. The structure-activity relationship of various YO compounds, novel plasmin inhibitors, in the apoptosis induction. Biochim Biophys Acta 2004;1674:291–298.

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