Fig. 5: The effect of an amide-to-ester substitution on cyclic hexapeptides with a hydrophilic residue and cyclic 8- and 9-mer peptides. | Nature Communications

Fig. 5: The effect of an amide-to-ester substitution on cyclic hexapeptides with a hydrophilic residue and cyclic 8- and 9-mer peptides.

From: Amide-to-ester substitution as a stable alternative to N-methylation for increasing membrane permeability in cyclic peptides

Fig. 5

a The structures of CP1 derivatives with a hydrophilic residue and their derivatives with an amide-to-ester substitution or an amide N-methylation. b The membrane permeabilities of the CP1 derivatives shown in Fig. 5a. N.D. denotes not detected. p (NH vs. O) < 0.0001, p (O vs. NMe) <0.0001 for CP1-Y1F-L2S. Note that the scale of the y-axis is different between the left and right graphs. c The structures of D8.31, D8.21, and D9.16, and their derivatives with substitution of an N-methylated amide with an amide (D8.31-amide, D8.21-amide, and D9.16-amide) or an ester (D8.31-ester, D8.21-ester, and D9.16-ester). d PAMPA of cyclic 8-mer and 9-mer peptides. The enlarged views of the results of D8.31 series and D9.16 series are shown in the insets. PAMPA was conducted with 3 μM compounds in PBS containing 5% DMSO and 16 h incubation at 25 °C. Each bar represents the mean value, and the error bars the standard deviation from experiments carried out in quadruplicate. p (D8.31-amide vs. D8.31-ester) = 0.0138, p (D8.31-ester vs. D8.31) = 0.0004, p (D8.21-amide vs. D8.21-ester) <0.0001, p (D8.21-ester vs. D8.21) = 0.0126, p (D9.16-amide vs. D9.16-ester) = 0.0003, p (D9.16-ester vs. D9.16) = 0.0002. All the P values were determined by a two-sided Welch’s t-test. **p < 0.01, *p < 0.05.

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