The development of methods for the separation, analysis and resolution of chiral drugs is ofimportant interest for pharmaceutical development. Two enantiomers of the same compound mayhave the same physical or chemical properties, but show marked differences in how they interactin a human system (i.e., regarding their pharmacology, toxicology, pharmacokinetics and metabolism). Thus, the chiral separation of drugs is important to eliminate the unwantedenantiomer from the preparation. Separation of enantiomers is typically achieved by high-performance liquid chromatography (HPLC) where a chiral selector is used in a chiral stationaryphase (CSP). CSPs can be composed of several types of molecules, including polysaccharides(i.e., amylose and cellulose) and proteins (e.g., albumin, enzymes), among others. Only a handfulof proteins have been investigated for use as HPLC CSPs despite their unique enantioselectiveproperties. Unfortunately current, protein-based CSPs have low loading capacity, are expensiveto prepare, and have limited stability. There is clearly a market need for enzyme and protein-based CSP separation methods with higher loading capacity, less degradation and extended shelflife. Based on market research interviews that we have conducted through NSF's I-Corps programon our platform biomaterial technology, it was made clear that the technology for chiral columnshas not changed and that innovation in the field was desired. Bondwell Technologies aims todevelop a novel high-capacity protein-based selector for use as a CSP based on our innovativebiomaterial. The unique qualities of our biomaterial addresses all of current limitations of chiralCBHs. During this proposed Phase I feasibility effort, we will first express the chiral selectorenzyme cellobiohydrolase (CBH I) and form our biomaterials, We will test the enzyme in thebiomaterial for function to ensure correct folding. We will then prepare our material to be used asa CSP. Finally, we will test for the ability of our biomaterial to separate enantiomers of the beta-bocking drugs, propranolol and alprenolol.
Public Health Relevance Statement: PROJECT NARRATIVE
The development of methods for the separation, analysis and resolution of chiral drugs is of
important interest for pharmaceutical development. Two enantiomers of the same compound may
have the same physical or chemical properties, but show marked differences when in a human
system (e.g., pharmacology, toxicology, pharmacokinetics and metabolism). Thus, the chiral
separation of drugs is important to eliminate the unwanted enantiomer from the preparation in the
interests of furthering drug safety.
Project Terms:
