Structural diversity of target-specific homopyrimidine peptide nucleic acid–dsDNA complexes

Abstract

Sequence-selective recognition of double-stranded (ds) DNA by homopyrimidine peptide nucleic acid (PNA) oligomers can occur by major groove triplex binding or by helix invasion via triplex P-loop formation. We have compared the binding of a decamer, a dodecamer and a pentadecamer thymine–cytosine homopyrimidine PNA oligomer to a sequence complementary homopurine target in duplex DNA using gel-shift and chemical probing analyses. We find that all three PNAs form stable triplex invasion complexes, and also conventional triplexes with the dsDNA target. Triplexes form with much faster kinetics than invasion complexes and prevail at lower PNA concentrations and at shorter incubation times. Furthermore, increasing the ionic strength strongly favour triplex formation over invasion as the latter is severely inhibited by cations. Whereas a single triplex invasion complex is formed with the decameric PNA, two structurally different target-specific invasion complexes were characterized for the dodecameric PNA and more than five for the pentadecameric PNA. Finally, it is shown that isolated triplex complexes can be converted to specific invasion complexes without dissociation of the Hoogsteen base-paired triplex PNA. These result demonstrate a clear example of a ‘triplex first’ mechanism for PNA helix invasion.

Disruption of Higher Order DNA Structures in Friedreich’s Ataxia (GAA)n Repeats by PNA or LNA Targeting

“…gamma-PNAs [47]). Additionally, long homopyrimidine PNAs (>15 nucleotides) can form regular triplex structures (PNA-triplexes) at physiologically relevant salt concentrations [48], whereas stable PNA-triplex and triplex-invasion complexes have not been reported for homopurine PNAs.…”

Synthesis of nucleobase-caged peptide nucleic acids having improved photochemical properties

“…Therefore, the intense band should be assigned as the triplex invasion complex (I) containing two PNA molecules. 21 Another band must be the conventional PNA-dsDNA triplex (T). However, formation of the triplex invasion complex was markedly suppressed when the dsDNA was incubated with 1 μM of the 16-mer cPNA (lane 7 in Fig.…”

Synthesis and Structure-Activity Studies of Peptide-Acridine/Acridone Conjugates

“…PNA consists of repeating Naminoethyl glycine units including peptide bonds but methylene carbonyl linkers constituted a connection between the particular nucleobases. Additionally, PNAs that distinct from DNA do not have any pentose sugar or phosphate groups [48][49][50]. Moreover, backbone of PNA is not gifted with any charges, therefore bindings between PNA and DNA are significantly stronger than between PNA strands or even DNA strands.…”

“…The effect of this reaction is the formation of triple-stranded complex which is built with PNA-DNA double duplex, formed by standard Watson-Crick hydrogen bonds with a second strand of PNA situated in the major groove of the duplex. That PNA strand is formed by the Hoogteen base parings which are hydrogen bonds between two identical molecules [48,49]. Hence, the design of PNA conjugates that intercalate to DNA and improve the properties of the helix formation are really reasonable.…”

“…Hence, the design of PNA conjugates that intercalate to DNA and improve the properties of the helix formation are really reasonable. The authors debated that PNAs, with their cationic nature improved the electrostatic affinity to DNA and also assured a high level of anionic structure of DNA [48,49,51].…”