Potentiometric Determination of Acid Dissociation Constants (p ) for an Anticancer Pyrrole-Imidazole Polyamide

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Nov 17

PMID 36385938

Authors

Xue Li

Zhaofang Shi

Tiezheng Jia

Affiliations

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Abstract

To optimize the pharmacological properties of an anticancer pyrrole-imidazole (Py-Im) polyamide (), we characterized the acid dissociation constants of , three other structurally related hairpin-shaped polyamides, and a cyclic polyamide bearing the same core sequence as 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 p of the -methylimidazole (Im) moieties varied with the peptide sequence and molecular architecture. A nearly 0.2 pH unit p shift of terminal Im toward the neutral state compared to internal Im was observed. Furthermore, according to the dissociation constants, a speciation diagram of as a function of pH is presented, which allows an assessment of the net charge and distribution of protonated species in the range of physiological pH.

Citing Articles

Cu (II)-catalyzed: synthesis of imidazole derivatives and evaluating their larvicidal, antimicrobial activities with DFT and molecular docking studies.

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PMID: 37980500 PMC: 10657005. DOI: 10.1186/s13065-023-01067-1.

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