Potentiometric Determination of Acid Dissociation Constants (p Ka) for an Anticancer Pyrrole-Imidazole Polyamide
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 pKof the N-methylimidazole (Im) moieties varied with the peptide sequence and molecular architecture. A nearly 0.2 pH unit pKshift of terminal Im toward the neutral state compared to internal Im was observed. Furthermore, according to the dissociation constants, a speciation diagram of PIP-1 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.
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[2022A1515011770] ; [2021B1515120046] ; [2020B121201002]
|WOS Research Area|
Pharmacology & Pharmacy
|WOS Accession No|
Cited Times [WOS]:0
|Document Type||Journal Article|
|Department||Department of Chemistry|
Research Center for Chemical Biology and Omics Analysis,Department of Chemistry,Guangdong Provincial Key Laboratory of Catalysis,Southern University of Science and Technology,Shenzhen,1088 Xueyuan Boulevard, Guangdong,518055,China
|First Author Affilication||Department of Chemistry|
|Corresponding Author Affilication||Department of Chemistry|
|First Author's First Affilication||Department of Chemistry|
Li，Xue,Shi，Zhaofang,Jia，Tiezheng. Potentiometric Determination of Acid Dissociation Constants (p Ka) for an Anticancer Pyrrole-Imidazole Polyamide[J]. ACS Medicinal Chemistry Letters,2022,13(11):1739-1744.
Li，Xue,Shi，Zhaofang,&Jia，Tiezheng.(2022).Potentiometric Determination of Acid Dissociation Constants (p Ka) for an Anticancer Pyrrole-Imidazole Polyamide.ACS Medicinal Chemistry Letters,13(11),1739-1744.
Li，Xue,et al."Potentiometric Determination of Acid Dissociation Constants (p Ka) for an Anticancer Pyrrole-Imidazole Polyamide".ACS Medicinal Chemistry Letters 13.11(2022):1739-1744.
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