Abstract
In recent times there has been an enormous rise in resistance to synthetic antibiotics as well as an increase in the virulence of bacteria, the so-called "superbugs". This problem has catalyzed a search for novel molecules to fight bacteria, which in turn relies on a better understanding of the molecular basis of the immune response. Beta-defensins are a class of small, cationic, cysteine-rich antimicrobial peptides expressed by humans and other animals to act against incoming pathogens. As well as their antimicrobial properties, beta-defensins also act as chemokines, recruiting cells to the sites of infection. Here the relationship between the tertiary structures of beta-defensin analogs and their chemotactic activities has been investigated using ion mobility-mass spectrometry (IM-MS) and biochemical assays. A panel of derivatives of the murine beta-defensin Defb14 has been formed and the ability of these peptides to chemoattract the receptor CCR6 has been assessed in vitro. The derivatives can be divided into two groups, those with chemotactic activity equal to that of the unmodified parent peptide, and those whose chemotactic activity has been lost upon modification. Analysis by ion mobility-mass spectrometry reveals the co...Continue Reading
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