Antimicrobial therapeutic enhancement of levofloxacin via conjugation to a cell‐penetrating peptide: An efficient sonochemical catalytic process

Herein, we make an effort to enhance the antimicrobial activity of levofloxacin (LVX) antibiotic via conjugation to a cell‐penetrating peptide (CPP) including Cys‐Gly‐Ala‐Phe‐Pro‐His‐Arg. For this purpose, cysteine is used as a linker between the LVX and CPP chain, and two heterogeneous nanoscale catalytic systems are employed as the substantial alternatives for traditional peptide coupling reagents like N,N,N′,N′‐tetramethyl‐O‐(benzotriazol‐1‐yl)uronium tetrafluoroborate (TBTU). Briefly, it has been found out that the antimicrobial potency of the synthesized CPP‐LVX conjugate (on the gram‐positive and gram‐negative bacteria) is noticeably enhanced (~20% more). It has been revealed via zone of inhibition (ZOI) and optical density (OD) evaluations. As a convenient method for making this type of the effective conjugations, ultrasound waves (with a specific frequency and power density) activate the catalytic sites of the heterogeneous nanoparticles. Through this synergistic effect, peptide/amide bond is formed during a short time (10 min), and high reaction yield (>90%) is obtained under mild conditions. Moreover, as a simple purification process, the catalyst nanoparticles are collected and separated through their high magnetic property.