Proteins used in drugs often react poorly to fluctuations in temperature and can degrade in storage. But researchers at UCLA have developed polymers that can stabilize the proteins during shipping, storage, and other activities.
Their instability means that proteins must be shipped and stored at regulated temperatures, increasing costs. Sometimes they must be discarded because their properties that make them effective degrade. In a study published in the Journal of the American Society of Chemistry, UCLA researchers describe how they synthesized polymers to attach to proteins to stabilize them during shipping and storage.
“Our polymers were synthesized by a controlled radical polymerization technique called reversible addition-fragmentation chain transfer polymerization in order to have end groups that can attach to proteins to form what is called a protein-polymer conjugate,” says Heather Maynard, a UCLA associate professor of chemistry and biochemistry, who worked on the project, in a press release. “We found that the polymers significantly stabilized the protein we used — lysozyme — better to lyophilization (freeze-drying, in which water is removed from the protein) and to heat than did the protein with no additives.”
The polymers are made with a polystyrene backbone and side chains of trehalose, a disaccharide found in various plants and animals that can live for long periods with very little or no water. These chemicals were employed in the 1960s with the popular “Sea Monkeys” kit. When the product was dropped into water, the powder became small shrimp whose long tails were said to resemble those of monkeys. Trehalose is an additive in several protein drug formulations, approved by the U.S. Food and Drug Administration, and known to stabilize proteins when water is removed.
The researchers found that attaching the polymer covalently (forming a protein-polymer conjugate) to the protein stabilized the protein to lyophilization better than adding the non-conjugated polymer at the same concentration. The team also found that the polymers stabilized the protein, lysozyme, significantly better than currently used stabilizers, such as polyethylene glycol, depending on the stress and conditions used.
Source: “UCLA researchers develop way to strengthen proteins with polymers,” UCLA Newsroom, 5/21/12
Image by Bmramon, used under its GNU Free Documentation license.
Dale McGeehon has been a journalist and editor for more than 25 years, covering chemical regulation and testing for Pesticides and Toxic Chemical News and innovations in material sciences for the National Technology Transfer Center. His writing credits include Omni and College Park magazines and The New York Times.