Our research on Peptide Nucleic Acids (abbreviated as PNAs) focuses on introducing chemical modifications that will make this class of molecules broadly useful to detect sequences of DNA. Unique DNA sequences are associated with diseases, pathogens, and many agents associated with bioterrorism. Detection of DNA from these agents can be employed as a method to detect their presence or absence. Our research involves the synthesis of a class of non-natural molecules (called PNAs) that bind to specific DNA sequences. We can design our molecules to bind to any sequence of DNA, and this past year we have found that our molecules are extremely good at selective recognition of DNA associated with anthrax. Currently, we are combining our molecules with detection devices to create a robust and reliable system for detection of anthrax and other pathogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK031143-01
Application #
7152073
Study Section
(LBC)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2005
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Zhang, Ning; Appella, Daniel H (2010) Advantages of peptide nucleic acids as diagnostic platforms for detection of nucleic acids in resource-limited settings. J Infect Dis 201 Suppl 1:S42-5
Englund, Ethan A; Appella, Daniel H (2007) Gamma-substituted peptide nucleic acids constructed from L-lysine are a versatile scaffold for multifunctional display. Angew Chem Int Ed Engl 46:1414-8
Zhang, Ning; Appella, Daniel H (2007) Colorimetric detection of anthrax DNA with a Peptide nucleic acid sandwich-hybridization assay. J Am Chem Soc 129:8424-5
Witschi, Mark A; Pokorski, Jonathan K; Appella, Daniel H (2006) Peptide nucleic acid microarrays made with (S,S)-trans-cyclopentane-constrained peptide nucleic acids. Methods Enzymol 410:189-200
Englund, Ethan A; Xu, Qun; Witschi, Mark A et al. (2006) PNA-DNA duplexes, triplexes, and quadruplexes are stabilized with trans-cyclopentane units. J Am Chem Soc 128:16456-7
Xu, Qun; Appella, Daniel H (2006) Practical synthesis of trans-tert-butyl-2-aminocyclopentylcarbamate and resolution of enantiomers. J Org Chem 71:8655-7
Pokorski, Jonathan K; Nam, Jwa-Min; Vega, Rafael A et al. (2005) Cyclopentane-modified PNA improves the sensitivity of nanoparticle-based scanometric DNA detection. Chem Commun (Camb) :2101-3
Guler, Mustafa O; Pokorski, Jonathan K; Appella, Daniel H et al. (2005) Enhanced oligonucleotide binding to self-assembled nanofibers. Bioconjug Chem 16:501-3
Englund, Ethan A; Appella, Daniel H (2005) Synthesis of gamma-substituted peptide nucleic acids: a new place to attach fluorophores without affecting DNA binding. Org Lett 7:3465-7