Svenson Johan, Brandsdal Bjørn-Olav, Stensen Wenche, Svendsen John S
Department of Chemistry, University of Tromsø, N-9037 Tromsø, Norway.
J Med Chem. 2007 Jul 12;50(14):3334-9. doi: 10.1021/jm0703542. Epub 2007 Jun 15.
The interactions between a range of small cationic antibacterial tripeptides and bovine and human serum albumin in a buffered aqueous solution at 25 degrees C have been studied using isothermal titration calorimetry. Results from the binding study indicate a single binding site on albumin with a dissociation constant between 4.3 and 22.2 microM for the different peptides. In a theoretical mouse model, a dissociation constant in this range corresponds to 95% albumin binding. The effect of this albumin interaction on the antibacterial capacity of the peptides against Staphylococcus aureus, strain ATCC 25923 was studied by including albumin in the assays at a 0.55 mM concentration. Presence of albumin induced a 10-fold increase of the minimal inhibitory concentration for the bulk of the peptides. Albumin itself has no effect on the bacterial growth and this increase is entirely ascribed to a strong competing protein binding. Collectively these results indicate that these antibacterial peptides do bind to albumin and that this binding strongly reduces the effective concentration of peptides available to combat bacteria.
