Negatively charged nucleic acids and phospholipid membranes

Negatively charged nucleic acids and phospholipid membranes represent fundamental structural targets characterized by their anionic surface charge. Nucleic acids, such as DNA and RNA, possess a polyanionic phosphate backbone, while certain phospholipid membranes, particularly those of bacteria, exhibit a high density of negatively charged headgroups like phosphatidylglycerol (Yeung et al., 2006, Science). These targets are primarily engaged through electrostatic interactions by cationic molecules, including antimicrobial peptides and cationic lipids (Zhdanov et al., 2002, Expert Opinion on Therapeutic Patents). In the context of infectious disease, drugs like polymyxins bind to the anionic lipid A component of Gram-negative bacterial membranes, causing physical disruption and cell death (Trimble et al., 2006, Cold Spring Harbor Perspectives). In biotechnology, cationic lipids are utilized to complex with negatively charged mRNA or DNA to form lipoplexes, facilitating cellular uptake and protection from degradation (Hou et al., 2021, Nature Reviews Materials). Targeting these structures is a key strategy in developing membrane-active antibiotics and advanced drug delivery systems. However, therapeutic application requires careful management of off-target toxicity to host cell membranes, which can lead to side effects like hemolysis or nephrotoxicity (Sahay et al., 2010, Nature Biotechnology).

Other names

Anionic biopolymersAnionic lipid bilayersPolynucleotides and anionic membranesAnionic macromolecular structures

Electrostatic interaction and binding to anionic phosphate or headgroups, leading to membrane disruption, intercalation, or molecular complexation.