open access: PLoS ONE: Proteins from Avastin® (bevacizumab) Show Tyrosine Nitrations for which the Consequences Are Completely Unclear

PLoS ONE: Proteins from Avastin® (bevacizumab) Show Tyrosine Nitrations for which the Consequences Are Completely Unclear

"......A major finding indicating pathogenetic or toxic properties of nitrated proteins was presented recently: assembly of alpha-synuclein and fibrinogen were deteriorated by nitration of only a small fraction of proteins [25], [32]. As for fibrinogen, nitration is accelerating the rate of fibrin clot formation [33]. It cannot be ruled out, therefore, that nitration of Avastin® may lead to side effects based upon probable disturbed protein-protein interactions as aggregations that in turn may lead to a series of complications as listed in the drug information sheet.
As to the underlying cause of tyrosine nitration it remains open, whether it can be considered as a post-translational modification of the immunoglobulin Avastin® or technical in nature, or both [34]-[38].
Taken together, it remains unclear if the observed nitrations and other PMs detected on Avastin® may be responsible for different biological or pharmacotoxicological properties and effects. Quantification of nitrations and their presence in several batches of the product has to be taken into considerations on probable toxicity as well, but corresponding in vivo analyses based upon these findings should be carried out by the manufacturers to probably save this protein drug that may have strong potential in tumor therapy."