Chemically Modified Peptide Nucleic Acids

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

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 nucleic acids and also to inspire new types of small molecule inhibitors for enzymes. Unique nucleic acid sequences are associated with diseases, pathogens, and many agents associated with bioterrorism. Detection of nucleic acids from these agents can be employed as a method to detect their presence or absence, as well as to monitor progression of a specific disease. Many diseases are also characterized by an overexpression of specific nucleic acid sequences. In cancer cells, the overexpression of a short RNA sequence, called a microRNA, has been linked to aggressive growth and survival. Our research involves the synthesis of a class of non-natural molecules (called PNAs) that bind to specific DNA or RNA sequences. We can design our molecules to bind to any sequence of DNA or RNA, and we have developed a new class of PNAs called thyclotides. We have recently published the manuscripts on thyclotides, describing how a thyclotide sequence can target a microRNA that is often overexpressed in cancer cells. We have continued to refine a novel detection assay using thyclotide molecules to detect HIV RNA. SARS-CoV-2 is also an RNA virus, and we are making new PNA probes to test for binding to target sequences. We also extended a study exploring the potential development of small molecule enzyme inhibitors, and we are trying to integrate our molecules into technological platforms for medical diagnostics.