Amanda Liu (Molecular and Cell Biology/Public Health major)
“Chemical Design, Synthesis, and Clinical Exploitation of Promising Ligands Having High Affinity for the TRP-M8 Receptor of Prostate Cancer Cells”
Sponsor: Ahamindra Jain, Lecturer, College of Chemistry
Project Description
Amanda will investigate a novel method of diagnosing, staging, monitoring, and treating prostate cancer. The specific phases of her investigation include optimizing the design and synthesis of N-radiofluoro or N-radioiodo-aryl-cycloalkylcarboxamides, which have high affinity for the TRP (transient receptor potential)-M8 receptor found in prostate cancer cells; and testing the affinity of the designed ligand for the TRP-M8 receptor in vitro and ultimately in vivo. One of the promising medical applications is the visualization of ligand-TRP-M8-receptor complex with PET or SPECT for diagnosis, staging, and monitoring prostate diseases. In contrast, current diagnostic methods are either inconclusive or painful. The ultimate goal is radiotherapy, a less invasive but more effective alternative to radical prostatectomy and brachytherapy. The process of optimizing the design and synthesis of the ligands and the medical exploitation of them will constitute Amanda’s senior honor’s thesis in MCB.
Scholar's Photo
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Amanda’s love-hate relationship with the silica gel column.
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Scholar's Journal
My lab-intensive summer was kicked off with a nice trip to the beautiful state of Utah, where the 39th National Organic Chemistry Symposium was held. In addition to sitting in interesting but way-over-my-head presentations by world renowned chemists, standing in front of my project poster, checking out research topics from all over the world (yes, some people came from other countries), my lab-mate and I got a tour to the salt lake and the copper mine. The majestic landscape in Utah strangely evoked the same awe in me as the intricate molecular interactions between receptors and ligands. After nearly a week of fresh air and gorgeous scenery, I returned to bottles of organic solvents, vials of chemicals, silica gel powder and more.
Latimer 302 was my second home during the summer, not that it was not so during the preceding spring semester. Seven or eight hours a day, five days a week, I was making, purifying, and identifying compounds. Getting the cooling sensation results of these compounds from Professor Wei marked several highlights of my summer. From each set of results, we gathered clues to steer the exploration--in search of molecules with potentially high affinity to TRPM8 receptors, over expressed on prostate cancer cells. Dr. Jain advised me on the techniques and procedures of making the ligands and helped me decipher complicated nuclear magnetic resonance spectra and mass spectrometry spectra. In the fifth week of summer research, D Alanine methyl ester conjugated to acid chloride rose above all others with promising results. Moreover, its superior cooling intensity and duration to the L configured isomer lead me to synthesize a series of D vs. L compounds, simultaneously exploring the effect of alpha-branching. Among this series of compounds, the only active ones, D and L Butyrolactone, contradicted my hypothesis that the L configuration fit the receptor better. Although such results dampened my spirits a bit, I was still making progress on my exploration. When I knew which path not to undertake, my chances at picking the rewarding path(s) increased. Towards the end of the summer, 4’ Aminoacetophenone conjugate emerged as the most active compound since Dr. Jain’s and professor Wei’s collaboration started several years ago! With great promise, this discovery accomplished the first step towards our ambitious goal-- letter-bomb radio-imaging or radio-therapeutic compounds.
All in all, I am grateful for this opportunity to single-heartedly pursue research over the summer. Thanks to the Haas Scholar Program’s ample funding and Dr. Jain’s, Professor Wei’s, and Edmundo’s guidance, support, and encouragement, I have grown tremendously as a researcher. Although there were days when I longed to be out of the fumes of neurological toxins and away in a beautiful foreign country like some of my fellow Haas scholars, I would not have exchanged my experience this past summer for any other =)
