Proteins are widely used as drugs — insulin for diabetics is the best known example — and as reagents in research laboratories, but they react poorly to fluctuations in temperature and are known to degrade in storage.
Because of this instability, proteins must be shipped and stored at regulated temperatures, resulting in increased costs, and sometimes must be discarded because their "active" properties have been lost. Manufacturers of protein drugs will generally add substances known as excipients, like polyethylene glycol, to the proteins to prolong their activity.
In a new study published in the Journal of the American Society of Chemistry (DOI: 10.1021/ja2120234), investigators from the UCLA Department of Chemistry and Biochemistry and the California NanoSystems Institute at UCLA (CNSI) describe how they synthesized polymers to attach to proteins in order to stabilize them during shipping, storage and other activities. The study findings suggest that these polymers could be useful in stabilizing protein formulations.
The polymers consist of a polystyrene backbone and side chains of trehalose, a disaccharide found various plants and animals that can live for long periods with very little or no water. An example many people will recognize is Sea- Monkeys — the 'novelty aquarium pet' introduced in 1962. Sea–Monkeys can be purchased as kits that contain a white powder; when water is added, the powder becomes small shrimp whose long tails are said to resemble those of monkeys.
Trehalose is known to stabilize proteins when water is removed, and as a result, it is an additive in several protein drug formulations approved by the Food and Drug Administration (FDA) to treat cancer and other conditions.
"Our polymers were synthesized by a controlled radical polymerization technique called reversible addition-fragmentation chain transfer (RAFT) polymerization in order to have end groups that can attach to proteins to form what is called a protein-polymer conjugate," said Heather Maynard, a UCLA associate professor of chemistry and biochemistry and a member of the CNSI. "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 research team found that attaching the polymer covalently to the protein — that is, forming a protein-polymer conjugate — stabilized the protein to lyophilization better than adding the non-conjugated polymer at the same concentration.
The team also found that the polymers stabilized lysozyme significantly better than the currently used excipients trehalose and polyethylene glycol, depending on the stress and conditions used.
The Maynard research group is currently exploring the use of their polymer as a stabilizer by attaching it or adding it to FDA–approved protein therapeutics. In addition, they are investigating the mechanism of how the polymer stabilizes proteins.
The research team included Rock J. Mancini and Juneyoung Lee, both graduate students of chemistry and biochemistry in the Maynard research group.
For more news, visit the UCLA Newsroom and follow us on Twitter.
Jennifer Marcus | EurekAlert!
Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
29.05.2017 | Physics and Astronomy
29.05.2017 | Physics and Astronomy
29.05.2017 | Earth Sciences