Disintegrin

Disintegrins are polypeptides from the venom of various vipers ( Viperidae ) were first isolated. The sequence is also found as a disintegrin domain in a series of human enzymes, the ADAM metalloproteases. To date, over 25 different disintegrins have been isolated from snake venom.

Construction

Disintegrins are water-soluble non-enzymatic cysteine-rich peptides, which exist in snake venom from 41-84 amino acids. In the ADAM proteases, the sequence of the disintegrin domain usually consists of about 90 amino acids. Almost all the disintegrins and disintegrin domains, such as ADAM15 also containing the RGD sequence (Arg -Gly-Asp ), which binds to, for example, integrins avb3. Other disintegrins of ADAM can bind to other Intgrine. ADAM28 binds to α4β1

In snake venom disintegrins which result in reduced blood coagulation by binding to the fibrinogen - binding receptor - integrin aIIbb3 - the platelets.

The RGD sequence, or as in the case of the KTS Obtustatin sequence is presented to the respective receptor at the end of a loop structure of the peptide.

Application

The highly specific binding to various receptors make the disintegrins for potential drugs to treat a number of diseases. The anticoagulant effect can be used for example for the prevention of thrombi. Worldwide, the disintegrins for the treatment of cancer, asthma and osteopenia are being tested.

Specifically, the high affinity for certain integrins in tumor growth important for the formation of new blood vessels (angiogenesis ) are ( for example avb3 ), is of interest.

Examples

Selection of some snake disintegrins.