Fig. 6: Impact of thioamide on hydrophilic macrocyclic peptide.
a The sequence of the cyclic hexapeptide analog of Somatostatin (13) and its mono-thioamidated regioisomers (13a–13f). b Partition coefficient of 13, 13a–13f in heptane-ethylene glycol (h/e) solvent system indicating their desolvation penalty. c Membrane permeability of the macrocyclic peptides determined by the PAMPA (Pe). Propranolol was used as the marker for transcellular transport. n = 3 ± SEM. Each bar represents mean values of three biological replicates: dots are individual data points. Statistical significance was measured against the (all-amide) parent molecule by a one-tailed unpaired t-test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns (non-significant) > 0.05. p (13 vs 13a, 13b, 13c, 13d, 13e, 13f) = 0.0002, <0.0001, 0.0052, 0.0002, 0.0020, 0.0005 for logD(h/e). p (13 vs 13a, 13b, 13c, 13d, 13e, 13f) = 0.0347, 0.0183, 0.2371, 0.0472, 0.2610, 0.3540 for Pe by PAMPA. Source data are provided as a Source Data file.
