Defensin

Defensins are small 33-47 amino acid long peptides having three intramolecular disulfide bridges. They occur in all animal organisms and higher plants and are used for defense against microbial pathogens, especially bacteria, but also fungi and toxins. In mammals they are found numerous on skin and mucosal surfaces and they form a large proportion of the proteins ( about 30%) in the granules of neutrophils. During an inflammatory response, the body's production of defensins increases.

Classification

Defensins can be divided based on their relationship into four families, each of which has its own entry in the membrane transport protein data bank: the animal defensins ( 1.C.19 ), the plant defensins ( 1.C.45 ), the insect defensins ( 1.C.47 ) and the pore-forming mammal -specific β -defensins ( 1.A.68 ).

Function

The mechanism of action of the defensins is not yet fully understood. It is known that defensins carry many cationic and hydrophobic amino acid residues. Such peptides are thus molecules are composed of two functional parts which interact with the positive charges and the negative charges of the pathogen membranes.

The preference of defensins applies membranes, which are characterized by a low content of cholesterol and thus differ from those of eukaryotic organisms. When they have passed through the membrane, they interact also with anionic molecules within the pathogen cell, such as DNA and RNA. Thanks to this relatively non-specific effect, the activity spectrum is wide ( broad spectrum antibiotic ) and it remains difficult for the pathogen to counteract the mechanism of defensins.

Surprisingly, it was found that the gene for dominant black coat color of the domestic dog also encodes a defensin named β -defensin 103 ( CBD103 ). This gene product binds to the melanocortin receptor 1, which is encoded by the Extension locus, and has a strong effect on the switching of eumelanin to pheomelanin.

Research

2001 was discovered the peptide Plectasin in a study of the Danish company Novozymes and described in 2005 in a publication that belongs as a defense molecule to the case of fungi from the order of peel fungus -like, animals and plants probably widespread so-called defensins. When now made ​​in elucidating its mode of action has been demonstrated that this drug with two effects triggers a defense against bacteria. Killing the pathogens on the one hand, in which the protein molecule attaches itself to the cell wall component of Lipid II and prevents that this is incorporated into new bacteria walls. On the other hand, alarmed and also at the same time it activates the immune system. Plectasin showed both in vitro and in an in vivo mouse model of infection, a particularly high effectiveness against pneumococci. Preclinical studies have also shown that multi-resistant bacteria had significant difficulty in developing this defensin against a resistance. The researchers will look amazing in this drug a promising lead compound for new antibiotics.

In current research, one tries to use the defensins as an antidote for example, against the bacterial anthrax toxin.