Aromatic Amide Foldamers as Cellular Transport Proteins
Ref: Iriondo-Alberdi, J., Laxmi-Reddy, K., Bouguerne, B., Staedel, C. and Huc, I. (2010), Cellular Internalization of Water-Soluble Helical Aromatic Amide Foldamers. ChemBioChem, 11: 1679–1685. doi: 10.1002/cbic.201000256
Summary: Foldamers are de novo peptides that can fold into conformations similar to that of native proteins without being susceptible to endogenous cellular processes like degradation. Since their advent, the range of potential uses for these synthetic peptides has been consistently broadening. Recent research (Iriondo-Alberti et al) has indicated one of these potential uses to be facilitating the transport of therapeutic drugs into the cell. Aromatic amide foldamers have been biologically evaluated as cell-penetrating agents, and I think a potentially cool research idea would be to take these characterized foldamers, study them in depth, and perhaps tinker with different mutations to try and increase their ability to traverse the cell membrane. Another consideration would be to try and test the foldamer’s transporting abilities with different drugs.
Optimization of Aptamer Regulation via 5' DNA Truncation
Ref: Belmont, B. and Niles, J. (2010), Engineering a Direct and Inducible Protein−RNA Interaction To Regulate RNA Biology. ACS Chemical Biology. 5 (9), 851-861. doi: 10.1021/cb100070j
Summary: RNA aptamers are chosen from randomly generated libraries of up to 100 base pairs based on specificity and binding affinity to certain ligands. Previous studies have explored the potential role of aptamers in transcriptional gene regulators, but their role in regulation at the translational level is relatively novel. It would be cool to explore the research conducted in the Niles lab in further detail by attempting to optimize their current TetR specific aptamer (Niles and Belmont 2010). At the moment, the one they have isolated decreases absolute expression of whatever gene it’s upstream of by 95% due to its presence alone. Truncating the gene at the 5’ end has shown promise: it destabilizes the secondary structure of the aptamer and allows the ribosome to bind more easily to the mRNA. Trying different 5’ truncations (both different base pairs and different truncation lengths) and examining their effect on both basal and inhibited (presence of TetR) expression levels would be an interesting topic to pursue.