Acid-base and lipophilic properties of peptide nucleic acid derivatives

Abstract

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.

Mucosomes: Intrinsically Mucoadhesive Glycosylated Mucin Nanoparticles as Multi‐Drug Delivery Platform

“…Previous experimental and theoretical studies on the ionization and lipophilic properties of PNA derivatives have proven PNA to be a hydrophilic macromolecule even though the backbone is not charged like DNA and RNA. [ 91,92 ] Given that mucin is densely coated with carbohydrate chains, which represent strong hydrophilic domains, it is reasonable to speculate that PNA binds mostly on the glycosylated portions of mucin through an H‐bonding mechanism. Similarly, even though albumin is a high molecular weight protein (66.4 kDa), HSA was encapsulated into mucosomes with an efficiency of 48%.…”