Wisconsin Alumni Research Foundation

Research Tools
Research Tools
New Amphiphiles for Manipulating Integral Membrane Proteins
WARF: P110170US02

Inventors: Samuel Gellman, Pil Seok Chae, Soren Rasmussen, Brian Kobilka

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a new class of amphiphiles that outperforms standard detergents in the manipulation of membrane proteins.
Overview
Integral membrane proteins are crucial cellular components, helping to transfer material and signals through the cytoplasm or between different cell compartments. Analyzing the structures and functions of these proteins is important for research and medicine. More than half of current pharmaceutical agents target integral membrane proteins.

Integral membrane proteins have large hydrophobic surfaces that are not compatible with watery environments. Amphiphilic detergents (containing both hydrophobic and hydrophilic regions) therefore are required to extract membrane proteins from the lipid bilayer and to hold the proteins in their natural shape. Detergents like dodecyl-β-maltoside (DDM) commonly are used but many membrane proteins denature and/or aggregate in response to such agents. Moreover, a vast number of amphiphiles are required to meet the needs for various proteins and applications. Only empirical testing allows researchers to identify useful amphiphiles for a particular need.

Desired are alternative amphiphilic ‘aids’ that can work to extract, stabilize and manipulate the huge diversity of membrane proteins in cells.
The Invention
UW–Madison researchers have developed new amphiphiles that better aid in the solubilization, isolation, purification, stabilization, crystallization and structural determination of integral membrane proteins.

The new molecules use a multifused ring system as a lipophilic group. They are synthesized from commercially available steroidal precursors (cholesterol, in most cases) and fall into two types – GLC and GCT amphiphiles.

Membrane preparations containing some protein of interest can be treated with the novel amphiphiles to achieve protein extraction and solubilization. The amphiphiles are able to stabilize membrane proteins for several weeks.
Applications
  • Agents for solubilization, isolation and other manipulation of membrane proteins and integral membrane proteins
  • Reagents for researchers conducting crystallography
  • Alternative biochemical detergents
Key Benefits
  • Outperform conventional detergents
  • Proteins remain stable for much longer.
  • No sacrifice in extraction efficiency
  • Work at lower concentrations
  • Effective with diverse group of membrane proteins
Stage of Development
Proteins extracted using the new amphiphiles have been shown to remain soluble for more than three weeks. Using DDM, stability decays within hours or days.
Additional Information
For More Information About the Inventors
Related Intellectual Property
For current licensing status, please contact Rafael Diaz at [javascript protected email address] or 608-960-9847

WARF