Acid-base and lipophilic properties of peptide nucleic acid derivatives.

The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid (PNA) derivatives, including eleven PNA monomers and two PNA decamers, is described. The acidity constants (pK a) of individual acidic and basic centers of PNA monomers were measured by automated potentiometric pH titrations in water/methanol solution, and these values were found to be in agreement with those obtained by MoKa software. These results indicate that single nucleobases do not change their pK a values when included in PNA monomers and oligomers. In addition, immobilized artificial membrane chromatography was employed to evaluate the lipophilic properties of PNA monomers and oligomers, which showed the PNA derivatives had poor affinity towards membrane phospholipids, and confirmed their scarce cell penetrating ability. Overall, our study not only is of potential relevance to evaluate the pharmacokinetic properties of PNA, but also constitutes a reliable basis to properly modify PNA to obtain mimics with enhanced cell penetration properties. [Display omitted] • The first study on acid-base and lipophilic properties of peptide nucleic acids (PNA). • pK a of acid-base centers of PNA evaluated by potentiometric method and MoKa prediction. • NMR experiments provide additional information on the protonation of PNA monomers. • Lipophilicity of PNA monomers and oligomers is investigated by IAM chromatography. • This study can lay the basis of evaluating the pharmacokinetic properties of PNA. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Pharmaceutical Analysis is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)