Effects of guanidino modified aminoglycosides on mammalian membranes studied using a quartz crystal microbalance

Abstract

The increase in bacterial and viral resistance to current therapeutics has led to intensive research for new antibacterial and antiviral agents. Among these, aminoglycosides and their guanidino derivatives are potent candidates targeting specific RNA sequences. It is necessary that these substances can pass across mammalian membranes in order to reach their intracellular targets. This study investigated the effects of the aminoglycosides kanamycin A and neomycin B and their guanidino derivatives on mammalian mimetic membranes using a quartz crystal microbalance with dissipation monitoring (QCM-D). Lipid bilayers as membrane models were deposited onto gold coated quartz crystals and aminoglycosides added afterwards. Notably, the guanidino derivatives exhibited an initial stiffening of the membrane layer indicating a quick insertion of the planar guanidino groups into the membrane. The guanidino derivatives also reached their maximum binding to the membrane at lower concentrations than the native compounds. Therefore, these modified aminoglycosides are promising agents for the development of new antimicrobial treatments.

Adsorption of Amyloidogenic Peptides to Functionalized Surfaces Is Biased by Charge and Hydrophilicity

“…To further detail the binding mechanisms of the peptides to the surfaces, QCM-D data for different frequency overtones (3rd, 5th, 7th, 9th, and 11th harmonic) can be used to sample varying distances from the sensor surface, especially for the soft LUB coated sensors. , The viscosity of the surface layer determines the penetration depths of the various overtones. The lower harmonics (3rd) probe distances further from the sensor surface while higher harmonics (11th) probe mass binding closer to the sensor surface (see Figure ).…”

“…Excess thiol was removed from the sensors by rinsing with isopropanol and the sensors were dried under a gentle stream of nitrogen gas. 49,50 Thiols quickly form dense SAM layers on gold sensors that reorganize its structure to increase density and minimize surface defects within several hours. 51 QCM-D Experiments and Data Analysis.…”

“…After rinsing with ultrapure water and isopropanol, the sensors were either dried under a gentle stream of nitrogen gas to use the unmodified gold sensors, or a self-assembled monolayer (SAM) of thiols was formed by immersing the sensors into a 1 mM solution of the respective thiol in isopropanol overnight (15–20 h). Excess thiol was removed from the sensors by rinsing with isopropanol and the sensors were dried under a gentle stream of nitrogen gas. , Thiols quickly form dense SAM layers on gold sensors that reorganize its structure to increase density and minimize surface defects within several hours …”

“…Data for the seventh harmonic were used for analysis in this study if not stated otherwise. Values for the third, fifth, seventh, ninth and 11th harmonic were used for depth profiling as different harmonics can probe different distances from the sensor surface, especially if coated with media of higher viscosity. , The fundamental frequency ( f 0 = f 1 = 5 MHz) was not used, as it is too noise-sensitive to flow changes within the cells . All frequency values (Δ f ) were normalized to the fundamental frequency (Δ f n /n ).…”

Amyloid aggregation and membrane activity of the antimicrobial peptide uperin 3.5

“…Each QCM‐D experiment was carried out using the Q‐Sense E4 (Q‐Sense, Stockholm, Sweden) system. In brief, sensors were cleaned, liposomes prepared ex situ and deposited onto the sensors to form a lipid bilayer as described previously …”