Complexation Of An Antimicrobial Peptide By Large-Sized Macrocycles For Decreasing Hemolysis And Improving Stability

Traditional macrocyclic hosts have finite cavity sizes, generally 5-10 angstrom, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water-soluble large-sized quaterphen[n]arenes (WQPns, n=3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants (K-a) of (4.20 +/- 0.23)x10(4) M-1 for PXG/WQP3 and (2.46 +/- 0.44)x10(5) M-1 for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host-guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.