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Carnegie Mellon Department of Chemistry

2011 Speakers & Abstracts

photo of Mehnaaz AliMehnaaz F. Ali, Xavier University of Louisiana

Modulation of Enzyme Activity via a Co-factor Mediated Trigger

The focus of this work is on the development of a sensor for the detection of biomarkers. Specifically aptamers, which are single stranded nucleic acid sequences that can be selected for a specific target analyte, will be used as the probe molecule. These sensors will link the recognition of a relevant analyte by an aptamer to the activation of glucose oxidase via its co-factor flavin adenine dinucleotide. By utilizing an enzyme-based detection module with high turnover rates, this sensor could provide excellent signal transduction and miniaturization capabilities. For our studies an aptamer selected against a model analyte will be used within a displacement assay. An analyte binding event will initiate a co-factor conjugated with a target analog to act as a trigger and activate a previously attenuated enzyme. To this end we show successful generation of apoenzyme with reproducible co-factor modulated signal generation. In addition, we have successfully completed the necessary functionalization of the enzyme cofactor for implementation of the displacement assay. Proof of concept studies includes an aptamer selected against model analytes L-tryptophan and thrombin with a co-factor modified analyte as the signal initiator. The combination of aptamer based target recognition with an enzyme derived signaling output will serve as an efficient tool for the sensitive and selective detection of relevant small molecules, proteins and nucleic acids.

photo of Massimiliano LambertoMassimiliano Lamberto, Monmouth University

Synthesis of Novel Telomerase Inhibitors: Development of Anticancer Therapeutics

The search for novel chemotherapeutic approaches for cancer treatment is an active research field. Recently, a new appealing target, the reverse transcriptase enzyme "telomerase", has attracted a lot of attention because this enzyme is over-expressed in 80-85% of cancer cell types and inactive in normal somatic cells. Telomerase is responsible for the synthesis of telomeric DNA and for maintaining the telomere length. It has been demonstrated that inhibition of telomerase induces cell senescence and death and, for this reason, it has become a very important target for cancer therapeutics. The synthesis and biophysical studies of novel telomerase inhibitors as potential anticancer therapeutics will be presented.

photo of Ioana E. PavelIoana E. Pavel, Wright State University

Raman and Surface-Enhanced Raman Spectroscopy for Medical and Biological Imaging: A Brief Retrospective and Applications

About 50 years after the discovery of the Raman scattering effect, the novel phenomenon of a strongly increased Raman signal from molecules attached to metallic nanostructures such as silver nanoparticles attracted considerable interest from both basic and practical viewpoints. This effect, known as surface-enhanced Raman scattering (SERS), shows promise in overcoming the low-sensitivity problems inherent in Raman spectroscopy. As a spectroscopic tool, SERS has the potential to combine the sensitivity of fluorescence with the structural information content of Raman spectroscopy. When new recent methods for determining SERS enhancement factors resulted in unexpectedly large factors of 14-15 orders of magnitude, the discrepancy between Raman-scattering cross sections and fluorescence cross sections was entirely overcome. That is, the detection of a single molecule with the high structural selectivity provided by its Raman spectrum became possible. Raman and SERS are predicted to have a huge impact on industry and research, however two of the most exciting and demanding applications involve medical diagnostic and biological imaging. A brief SERS retrospective and several applications involving Raman imaging of bone tissue, SERS-based label free detection of proteins at very low concentrations and molecular fingerprinting of cells will be presented. The toxicity aspects of the silver nanomaterials used in these SERS applications will also be discussed.