NOVELTY: This technology comprises a novel method to introduce polar and ionizable groups into the interior of proteins without the loss of protein stability.
VALUE PROPOSITION: Currently, the loss of stability related to the introduction of internal ionizable groups has plagued efforts in protein engineering. The disclosed technology overcomes the current limitation by successful and easy introduction of polar and ionizable groups into the hydrophobic interior of a protein without any special structural adaptation and without loss of the protein stability. The other features of the technology include:
• Proteins do not change conformation and remain folded after the engineered internal ionizable groups become charged.
• Internal ionizable groups can be used to modify the stability of proteins in response to changes in pH.
• The technology can be used to reach new heights in protein engineering through design of novel enzymes and switches that can be used to alter the stability and properties of proteins upon exposure to specific values of pH.
TECHNICAL DETAILS: JHU scientists have developed a novel method that allows the stable introduction of polar and ionizable groups into the interior of proteins. Specifically, the researchers substituted 25 internal residues in a protein with basic or acidic ones, one at a time, to verify the possibility of introduction of ionizable groups inside the protein without the loss of stability. They have also demonstrated that the increase in stability of a protein is the property that needs to be modulated to allow substitution of internal residues with polar or ionizable ones without loss of the native conformation.
LOOKING FOR PARTNERS: To develop and commercialize the technology as an efficient research tool to engineer novel enzymes and to build switches that can be used to modify the stability of proteins in response to changes in pH.
PATENT STATUS: Granted US Patent
9,499,580STAGE OF DEVELOPMENT: Discovery
DATA AVAILABILITY: Under CDA/NDA
PUBLICATIONS: PNAS. 107, 37 ,
Biochemistry. 18;49(19):4138-46 ,
PNAS, 108, 13
