HeX-Bond for Molecular Engineering


Available for Licensing

IP Status

US Utility Patent Pending: US 2019/0382747 A1


Pui S. Ho
Anna-Carin Carlsson
Matthew Scholfield
Melissa Coates Ford
Rhianon Kay Rowe
Austin Alexander
Ryan Mehl

At A Glance

The construction of more stable proteins is important in biomolecular engineering, particularly in the design of biologics-based therapeutics.

CSU researchers have for the first time demonstrated that a halogen bond (XB) can be engineered to stabilize and increase the activity of an enzyme, with the increased stabilizing potential of the HeX-B further extending the application of halogenated amino acids in the design of more stable protein therapeutics.


Licensing Director

Steve Foster

Reference No.: 17-096

Technology Overview

Investigators at Colorado State University have discovered a new form of a non-covalent interaction, which is named a hydrogen bond enhanced halogen bond (or HeX-B, for short). The HeX-B was engineered into the enzyme lysozyme to increase the thermal stability of a commonly used enzyme by 1°C and the activity by 15% at elevated temperatures relative to the native enzyme. This interaction can be used to increase the stability of enzymes and proteins by 1 to 3.5 kcal/mol. This interaction, therefore, can be translated to significant increases in stability of proteins at high temperatures for biomolecular engineering halogenated proteins and nucleic acids. This process can also increase the affinity of an inhibitor or drug against therapeutic targets by 5 to >300-fold when designing new halogenated compounds for clinical use.


Current state-of-the-art relies on stand alone, classical halogen bonding interactions, which can provide 1 to 6 kcal/mol of stabilizing energy to a system.  The HeX-B provides an additional 1 to 4 kcal/mol stabilizing energy, which translates to significant increases in thermal stability of molecules and in affinity for halogenated compounds.

  • Molecular engineering
  • Medicinal chemistry
  • Materials chemistry
  • Biological engineering
  • Chemical engineering

Carlsson, Anna-Carin C, et al. “Increasing Enzyme Stability and Activity through Hydrogen Bond-Enhanced Halogen Bonds.” Biochemistry, American Chemical Society, 17 July 2018, www.ncbi.nlm.nih.gov/pubmed/29921126.

Last updated: March 2020