Potentiometric Determination of Acid Dissociation Constants (pK _a) for an Anticancer Pyrrole-Imidazole Polyamide.

ABSTRACT: To optimize the pharmacological properties of an anticancer pyrrole-imidazole (Py-Im) polyamide (PIP-1), we characterized the acid dissociation constants of PIP-1, three other structurally related hairpin-shaped polyamides, and a cyclic polyamide bearing the same core sequence as PIP-1 via potentiometric titration. The acidities of the carboxylic acid at the C-terminus and the tertiary amine in the triamine linker remained very similar among the polyamides tested, whereas the pK _a of the N-methylimidazole (Im) moieties varied with the peptide sequence and molecular architecture. A nearly 0.2 pH unit pK _a shift of terminal Im toward the neutral state compared to internal Im was observed. Furthermore, according to the dissociati

SUBMITTER: Li X 

PROVIDER: S-EPMC9661695 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature