Drug Conjugation Induced Modulation of Structural and Membrane Interaction Features of Cationic Cell-Permeable Peptides

摘要: Cell-penetrating peptides might have great potential for enhancing the therapeutic effect of drug molecules against such dangerous pathogens as Mycobacterium tuberculosis (Mtb), which causes a major health problem worldwide. A set cationic cell-penetration with various hydrophobicity were selected and synthesized carrier isoniazid (INH), first-line antibacterial agent tuberculosis. Molecular interactions between their INH-conjugates cell-membrane-forming lipid layers composed DPPC mycolic acid (a characteristic component Mtb cell wall) evaluated, using Langmuir balance technique. Secondary structure INH conjugates was analyzed compared to that native by circular dichroism spectroscopic experiments performed in aqueous membrane mimetic environment. correlation found conjugation induced conformational affinity changes INH–peptide conjugates. The degree mode interaction also characterized AFM imaging penetrated layers. In vitro biological evaluation Penetratin Transportan Results showed similar internalization rate into EBC-1 human squamous carcinoma, but markedly different subcellular localization activity on intracellular Mtb.