Researchers at MetaPhore Pharmaceuticals have used computer aided design techniques to achieve a hundred-fold increase in the catalytic activity of one of the companys synthetic manganese-based compounds previously shown to exert protective anti-inflammatory effects in animal models.
The compounds, part of a family being developed by Metaphore, mimic the action of the bodys prime free radical fighting natural enzyme, superoxide dismutase (SOD). The original SOD mimetic compound developed by Metaphore achieved catalytic rates approaching natural SOD.
The improved compound possesses the highest catalytic rate for superoxide dismutation of any known synthetic mimetic, said lead researcher, Dennis Riley, adding that the improved compound also exceeds the catalytic rate of natural copper, zinc and manganese SOD enzymes because it actually increases in catalytic rate as the pH decreases.
In a study published this month by the journal Inorganic Chemistry, the researchers also reported that the improved SOD enzyme mimetic, consistent with its enhanced catalytic rate, exhibited protective effects in animal models of reperfusion injury and septic shock at dosage levels one hundred times less than those required using the original SOD enzyme mimetic.
The lower dosage plus retention of the originals high degree of stability makes the improved SOD mimetic an even more attractive candidate for use as a drug in humans.
Riley and his team used computer-aided design processes, developed based on their unique understanding of how the original SOD mimetic functions as a catalyst, to circumvent the time consuming and expensive process of synthesizing and then testing countless molecular variations.
Once we understood the subtle and unobvious interplay between position, number and spatial arrangement of atoms and groups in dictating a molecules catalytic activity, we were able to design highly complicated molecules and test their potential as catalysts,
Contact: Punnie Donohue
Kupper Parker Communications