James Greisler '10 (Galway, N.Y.) and Elijah LaChance '10 (Williston, Vt.) spent their summer working on two different carbohydrate (i.e. sugar) research projects under the advisement of Nicole Synder, assistant professor of chemistry. The first project focused on the synthesis of septanoses (seven-member ring sugars that do not appear in nature) while the second project involved the creation of safer, more effective derivates of a potent anti-tumor agent. In general, both projects involved the preparation and characterization of designed structures that incorporate unnatural and natural carbohydrates, which can subsequently be used to investigate a number of key carbohydrate interactions of biological interest.
In their first project, Greisler and LaChance tried to make septanoses from other naturally-occurring sugars, such as glucose, galactose, mannose, and 2-deoxyglucose. Their basic strategy involved breaking open the rings of the natural sugars (which contain six carbon atoms), adding another carbon atom to them, and then fusing the rings back together. For the most part, Greisler and LaChance were moving into new territory with their project because very little literature has been published regarding the synthesis of seven-member ring sugars. This dearth of information on the topic is primarily a consequence of the difficulties in making septanoses, especially the fact that such projects are expensive and yield little product. These two researchers hope that their efforts will help to optimize existing synthetic routes for the preparation of these unnatural carbohydrates and make their creation more cost effective.
According to Greisler and LaChance, the septanose project could have broad applications to the design of new pharmaceuticals. One of the greatest challenges associated with drug design is keeping up with natural selection and evolution. Many strains of bacteria and viruses have become resistant to current therapies, rendering those medications ineffective at treating disease and infection. Since the molecules used in pharmaceuticals do not have the capability to change like the living organisms they are combating, scientists are forced to constantly engineer new molecules for use in the next generation of drug therapies. The unnatural carbohydrates being developed by Greisler and LaChance could help to give drug designers an edge in this struggle. Septanoses have a lower conformational energy than more commonly used sugars, making them more stable and better able to interact with other biomolecules. As a result, they could be substituted into drugs so that the drugs are not recognized by infectious agents.
Greisler and LaChance's second project involved synthesizing novel derivates of cisplatin, an effective anti-tumor agent used to treat a number of different types of cancer, such as cervical, testicular, and ovarian cancer. Unfortunately, cisplatin has a number of drawbacks that limit or prohibit its use in certain patients. These drawbacks include severe toxic side effects, resistant tumor cell lines, and a narrow therapeutic index. Greisler and LaChance aimed to make several different types of cisplatin derivates that reduced unwanted side effects and treated cisplatin-resistant tumor strains. The derivates they prepared over the summer are unique compared to the derivates being pursued by other researchers in that they are the first examples of cisplatin derivates to incorporate a carbohydrate-based enediyne group.
While their efforts over the summer certainly made great contributions to the project, Greisler and LaChance stress that the project is still in its preliminary stages and more work will still be needed to be done in the future. Indeed, ongoing research in Prof. Synder's lab will continue to focus on the synthesis, characterization, and biological evaluation of these cisplatin derivates. The knowledge gained through these continuing studies will serve to further a general understanding of the anti-tumor properties of cisplatin derivatives and build a foundation for the rational design of derivates that can specifically target certain cancer types.
Greisler is considering a chemistry and theater double major. He plays the trumpet in the brass ensemble and is actively engaged in many theater department activities. LaChance is a neuroscience major and biology minor. On campus, he serves as the editor of the science and technology section of The Spectator, the secretary of the Biomatters Club, and a member of the Christian Fellowship. He also sings in the Oratorio Society and plays the trumpet in the orchestra, brass ensemble, jazz band, and jazz combo. In addition to his research project, LaChance also wrote student research articles for the Hamilton Web site over the summer.
-- by Nick Berry '09
In their first project, Greisler and LaChance tried to make septanoses from other naturally-occurring sugars, such as glucose, galactose, mannose, and 2-deoxyglucose. Their basic strategy involved breaking open the rings of the natural sugars (which contain six carbon atoms), adding another carbon atom to them, and then fusing the rings back together. For the most part, Greisler and LaChance were moving into new territory with their project because very little literature has been published regarding the synthesis of seven-member ring sugars. This dearth of information on the topic is primarily a consequence of the difficulties in making septanoses, especially the fact that such projects are expensive and yield little product. These two researchers hope that their efforts will help to optimize existing synthetic routes for the preparation of these unnatural carbohydrates and make their creation more cost effective.
According to Greisler and LaChance, the septanose project could have broad applications to the design of new pharmaceuticals. One of the greatest challenges associated with drug design is keeping up with natural selection and evolution. Many strains of bacteria and viruses have become resistant to current therapies, rendering those medications ineffective at treating disease and infection. Since the molecules used in pharmaceuticals do not have the capability to change like the living organisms they are combating, scientists are forced to constantly engineer new molecules for use in the next generation of drug therapies. The unnatural carbohydrates being developed by Greisler and LaChance could help to give drug designers an edge in this struggle. Septanoses have a lower conformational energy than more commonly used sugars, making them more stable and better able to interact with other biomolecules. As a result, they could be substituted into drugs so that the drugs are not recognized by infectious agents.
Greisler and LaChance's second project involved synthesizing novel derivates of cisplatin, an effective anti-tumor agent used to treat a number of different types of cancer, such as cervical, testicular, and ovarian cancer. Unfortunately, cisplatin has a number of drawbacks that limit or prohibit its use in certain patients. These drawbacks include severe toxic side effects, resistant tumor cell lines, and a narrow therapeutic index. Greisler and LaChance aimed to make several different types of cisplatin derivates that reduced unwanted side effects and treated cisplatin-resistant tumor strains. The derivates they prepared over the summer are unique compared to the derivates being pursued by other researchers in that they are the first examples of cisplatin derivates to incorporate a carbohydrate-based enediyne group.
While their efforts over the summer certainly made great contributions to the project, Greisler and LaChance stress that the project is still in its preliminary stages and more work will still be needed to be done in the future. Indeed, ongoing research in Prof. Synder's lab will continue to focus on the synthesis, characterization, and biological evaluation of these cisplatin derivates. The knowledge gained through these continuing studies will serve to further a general understanding of the anti-tumor properties of cisplatin derivatives and build a foundation for the rational design of derivates that can specifically target certain cancer types.
Greisler is considering a chemistry and theater double major. He plays the trumpet in the brass ensemble and is actively engaged in many theater department activities. LaChance is a neuroscience major and biology minor. On campus, he serves as the editor of the science and technology section of The Spectator, the secretary of the Biomatters Club, and a member of the Christian Fellowship. He also sings in the Oratorio Society and plays the trumpet in the orchestra, brass ensemble, jazz band, and jazz combo. In addition to his research project, LaChance also wrote student research articles for the Hamilton Web site over the summer.
-- by Nick Berry '09
