Graduate student Eden Reichard will present
"Peptide-based Biosensors: Designs and Applications in Clinical Diagnostics"
on October 31, 2017 at 4:10 PM in Neville Hall, Room 3.
Abstract:
The development of biosensors continues to provide practitioners with sensitive, quick, and versatile tests for the detection of disease. Peptides are common components in biological analysis due to their diversified sequences, relative stability, and established solid-phase synthesis protocols. Currently, a wide variety of peptide-based sensors exist for the rapid detection of nucleic acids, small molecules, metallic ions, and enzymes. Proteases are an enzymatic target of interest in biological systems given their central role in cell behavior. Sensitive and specific peptide-based probes are needed for the detection of protease-associated disease.
In my seminar, I will discuss the development of three different cleavable peptide probes. In the first study, a peptide sensor is coupled to denatonium and designed as an insoluble chewing gum. Upon cleavage by a matrix metalloproteinase, which is upregulated in peri-implantitis, the bitter compound is released alerting the patient of the disease. In the second study, a near-infrared fluorophore labeled pro-peptide is designed specifically for the recognition of active thrombin. Thrombin is the pivotal protease in the blood coagulation process. This strategy allows for the non-invasive imaging of pulmonary embolism. In the third study, an activatable cell-penetrating peptide was synthesized for the detection of reactive oxygen species (H202). In this case, the reaction between hydrogen peroxide and a boronic acid linker in the peptide results in spontaneous cleavage, highlighting that proteases are not required to utilize cleavable peptides as biosensors.
References:
Weinstain, R.; Savariar, E. N.; Felsen, C. N.; Tsien, R. Y. J. Am. Chem. Soc. 2014, 136(3), 874-877 Ritzer, J.; Lühmann, T.; Rode, C.; Pein-Hackelbusch, M.; Immohr, I.; Schedler, U.; Thiele, T.; Stübinger, S.; Rechenberg, B. V.; Waser-Althaus, J.; Schlottig, F.; Merli, M.; Dawe, H.; Karpisek, M.; Wyrwa, R.; Schnabelrauch, M.; Meinel, L. Nat. Commum. 2017, 8 (1), 264 Page, M. J.; Lourenco, A. L.; David, T.; LeBeau, A. M.; Cattaruzza, F.; Castro, H. C.; VanBrocklin, H. F.; Coughlin, S. R.; Cralk, C. S. Nat. Commun. 2015, 6 (1), 8448