Tri-functionalized cryptophane biosensors for biomolecular imaging and MRI diagnostics

Cryptophanes with high xenon affinity enable ultrasensitive detection of analytes in solution using Xe-129 NMR/MRI

Technology Overview: 

The Dmochowski Lab has developed biosensors comprised of tri-functionalized cryptophane with high affinity for hyperpolarized 129Xe.  These biosensors can be designed to detect molecular markers associated with cancer and other disease. More specifically, a biosensor has been synthesized that detects matrix metalloproteases (MMPs), which are frequently upregulated in many cancers. 

The MMP enzyme cleaves the peptide covalently attached to the 129Xe biosensor, resulting in a change in the chemical environment of 129Xe readily detectable by a 0.5 ppm chemical shift in NMR. The features of these tri-functionalized cryptophanes enable the detection of picomolar concentrations of cryptophane biosensors by a technique known as Hyper-CEST NMR/MRI.  Additional xenon biosensors have been designed to target integrin receptors, folate receptor, and carbonic anhydrase. In most cases, binding the cryptophane biosensor to its protein target produces a measureable change in the Xe-129 NMR chemical shift.

From Khan et al, 2015. Folate-conjugated cryptophane to target cryptophane to membrane-bound folate receptors that are overexpressed in many human cancers.

Advantages: 

• Tri-functionalized cryptophanes well-solubilized in water
• Highest known affinity for xenon
• Very favorable Xe exchange kinetics
• Ultrasensitive analyte detection
• Tri-functionalized cryptophane biosensors can be designed that each yield distinct 129Xe NMR chemical shifts and can be targeted to different biomarkers

Applications: 

• Biosensors
• 129Xe MRI diagnostics next-generation platform
• Biomolecular imaging and enhancement of existing 1H MRI technology

Stage of Development: 

In vitro proof-of-concept testing

Intellectual Property: 

US 8,222,022 

Reference Media: 

• Riggle B.A. et al.  J Am Chem Soc, 2015 Apr 29, 137(16): 5542.
• Taratula O. et al.  Supramol. Chem., 2015 Jan 1, 27(1-2): 65.
• Khan N.S. et al.  Bioconjugate Chem., 2015, 26(1): 101.
• Taratula O. et al.  Org Lett, 2012 July 20, 14(14): 3580.
• Taratula O. et al.  Org Lett, 2011 Mar 18, 13(6): 1414.
• Bai Y. et al.  Anal Chem, 2012 Nov 20, 84(22): 9935.
• Hill PA et al.  J Am Chem Soc, 2007 Aug 1, 129(30): 9262.

Desired Partnerships: 

• License
• Co-development

Docket # T4532