The software, known as "Disulfide by Design,” aims to help companies engineer disulfide bonds to increase stability, which, “in general, means longer bioactivity under a greater range of cellular conditions, and potentially greater shelf-life,” Alan Dombkowski, PhD, inventor of the software and professor of toxicology and pharmacology at Wayne State University, told BioPharma-Reporter.com.
More specifically, the web-based software looks to “identify potential disulfides by considering the geometric relationships in ‘native’ disulfides and extending them to the desired target protein,” Dombkowski said.
“In other words, characteristics of disulfides found naturally are used in the prediction. Using atomic coordinate data from native disulfides, I devised the algorithm to predict where we might insert a new one that would conform to the geometric constraints,” he added.
As far as the types of uses for the software, which has been cited in more than 40 scientific publications since 2002, Dombkowski said he believes there’s a range of possibilities.
“There is a great deal of interest in using antibodies as therapeutics in a wide range of diseases, including cancer. The stability of protein-based therapeutics, such as antibodies, is very important. Proteins are susceptible to degradation and proteolytic cleavage which clear them from the blood stream and reduces their half-life,” he said.
He gave the example of the disulfide engineering approach by Novo Nordisk, which is creating “a more stable growth hormone, filed in a patent application.”
There are a number of ways to increase protein stability, “including the addition of salt bridges, random mutations that are then selected for increased stability (directed evolution), and other approaches,” Dombkowski said, noting that all “are still very challenging and require further development to meet the needs of industry.”
Other companies have requested information about the software recently, Dombkowski added.