Engineering student's research may lead to improved drugs with no side effects
AN undergraduate has published a paper in a Journal of Chromatography A, a Tier-1 journal -- and as the lead writer to boot. Joel Yong (picture above), 4th year Chemical and Biomolecular Engineering student, wrote the paper with his two supervisors, Dr Xiao Youchang and Prof Neal Chung. Entitled "The facile synthesis of an aldehyde-containing graft copolymer membrane for covalent protein capture with retention of protein functionality", his paper describes a novel method using membrane technology to retain the functions of an immobilised protein for use as an agent to separate chiral molecules. It was written as part of the requirements of an Independent Study Module that he took under the umbrella of the University Scholars Programme which provided him the opportunity to undertake such academically-rigorous projects independently as well as to contribute to his supervisors' works.
Chiral compounds have both "left-handed" and "right-handed" molecules known as "enantiomers", which are mirror images of each other. It is usually the case that only one of these enantiomers provides a therapeutic effect, while the other enantiomer may be biologically inactive or even be toxic to the human body. For example, in the case of thalidomide, a drug used for sedative purpose in the 1950s, the right-handed molecule induces foetal malformation, while the left-handed molecule was able to cure morning sickness. Regulatory standards are now shifting towards the development of "enantiopure" drugs -- the useful enantiomer is present while the undesirable enantiomer is absent from the final product that can be sold off-the-counter at pharmacies.
Joel explains that retaining the functionality of biomolecular proteins which have been immobilised on an insoluble carrier surface has always been a researcher's challenge, as proteins tend to lose their activity upon immobilisation due to a change in their structures. However, there is now a wide body of literature available on the single-layer immobilisation of proteins onto a carrier surface through methods like physical adsorption, while multiple chemical reactions must be carried out to prepare the final substrate if a multi-layered binding is required.
The best immobilisation, nevertheless, is arguably derived from a chemical coupling of the protein to the carrier surface. On one hand, researchers have developed single-layered chemical coupling and multi-layered physical adsorption of the protein, but there have been no methods thus far to develop a multi-layered chemical coupling of proteins to a carrier surface. Joel’s method involves a fusion of those ideas to chemically couple proteins to the carrier surface in multi-layers.
For his research, Joel synthesised a novel polymeric membrane containing aldehydes grafted onto a polyvinylidene fluoride backbone in multi-layers through a method known as atom transfer radical polymerisation. These multi-layered aldehydes could then chemically couple the protein to the membrane. Joel then demonstrated that the resultant protein-bound membrane could retain the separation efficacy of the free BSA in the chiral separation of a racemic tryptophan mixture.
Said his supervisor, Prof Neal Chung, who is known for his expertise in membrane technology: "Together with Dr Xiao, Joel has discovered a new synthesis approach for protein adsorption and separation. Joel has put in a lot of effort and his own ideas. He is a unique and exceptional student."
As to the applications of his novel method, Joel said, "This work may pave the way for future research on the separation of chiral compounds. What we aim to do is to produce novel membranes that can carry out such separations, as they are much less energy-intensive than current industrial liquid chromatography operations. We do know that energy concerns in future will be much greater especially with the impending depletion of fossil fuels. At the present moment, however, the capital cost of procuring membranes is still much higher than conventional liquid chromatography equipment."
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