A.K Manukyan
CUNY Hostos Community College,
United States
Keywords: peptide nucleic acid (PNA), chiral backbone modifications, PNA/DNA and PNA/RNA binding stability, therapeutic and diagnostic applications
Summary:
Peptide Nucleic Acid (PNA) is a synthetic nucleic acid analog in which the conventional sugar-phosphate backbone is replaced with a pseudopeptide chain comprising aminoethylglycine units. This unique architecture allows PNA to hybridize with both DNA and RNA with high affinity and specificity. To further enhance the binding affinity and sequence selectivity of PNA, structural modifications introducing chirality into the backbone have been investigated. Notably, studies have shown that substituting the ethylenediamine moiety with cyclopentyl units or incorporating (R)- or (S)-configured chiral centers into specific backbone positions markedly improves binding properties. This research integrates computational approaches to analyze the stability and structural dynamics of PNA and its modified analogs, including cyclopentyl-PNA and chiral-PNA variants, in complex with DNA and RNA. The findings indicate that these specific structural modifications enhance the thermodynamic stability of PNA/DNA and PNA/RNA complexes. Additionally, entropy contributions and dihedral angle preferences play a significant role in the observed stronger binding interactions. These insights are instrumental in guiding the design of next-generation PNA molecules with optimized biophysical properties, paving the way for advancements in therapeutic and diagnostic applications.