Structural Preorganization of Peptide Nucleic Acids: Chiral Cationic Analogues with Five- or Six-Membered Ring Structures

Kumar, Vaijayanti A.

doi:10.1002/1099-0690(200207)2002:13<2021::aid-ejoc2021>3.0.co;2-9

Cited by 64 publications

(6 citation statements)

References 56 publications

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“…In order to formulate conclusions from our experimental results, it is necessary to understand the role played by the conformation resulting from the syn / anti PNA structure. Indeed, previous studies demonstrated the benefit of including one or several asymmetric64–66 site(s) into an aeg PNA (Table 1). In the present study, PNAs present two chiral centers in their amt unit (Table 1).…”

Section: Resultsmentioning

confidence: 99%

Charge dependent behavior of PNA/DNA/PNA triplexes in the gas phase

Delvolvé¹,

Tabet²,

Bregant³

et al. 2006

J. Mass Spectrom.

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Intact noncovalent complexes were studied in the gas phase using negative ion nano-ESI mass spectrometry. Among various noncovalent systems studied in the gas phase, the interaction of DNA strands with peptide nucleic acids (PNAs) presents a strong interest as biologically relevant systems. PNAs originally described by Nielsen are used as DNA mimics as possible medical agents by imprisoning DNA single strands into stable noncovalent complexes. Two types of PNAs were investigated in the PNA/DNA multiplex: the original Nielsen's PNA and a modified backbone PNA by the introduction of syn- and anti-(aminoethyl)thiazolidine rings. We first investigated the stoichiometry of PNA/DNA multiplexes formed in solution and observed them in the gas phase via qualitative kinetics of complementary strand associations. It resulted in observing PNA2/DNA triplexes (ts) as the multiply deprotonated species, most stable in both the solution and gas phase. Second, charge-dependant decompositions of these species were undertaken under low-energy collision conditions. It appears that covalent bond cleavages (base releasing or skeleton cleavage) occur from lower ts charge states rather than ts unzipping, which takes place from higher charge states. This behavior can be explained by considering the presence of zwitterions depending on the charge state. They result in strong salt-bridge interactions between the positively charged PNA side chain and the negatively charged DNA backbone. We propose a general model to clearly display the involved patterns in the noncovalent triplex decompositions. Third, the relative stability of three PNA2/DNA complexes was scrutinized in the gas phase by acquiring the breakdown curves of their ts(6-) form, corresponding to the ts unzipping. The chemical structures of the studied PNAs were chosen in order to evidence the possible influence of backbone stereochemistry on the rigidity of PNA2/DNA complexes. It provided significantly different stabilities via V(m) measurements. The relative gas-phase stability order obtained was compared to that found in solution by Chassaing et al., and shows qualitative agreement.

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Section: Resultsmentioning

confidence: 99%

Charge dependent behavior of PNA/DNA/PNA triplexes in the gas phase

Delvolvé¹,

Tabet²,

Bregant³

et al. 2006

J. Mass Spectrom.

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“…The current limitations in PNA properties (Figure ) are its poor water solubility and lack of cell permeability coupled with ambiguity in DNA/RNA recognition arising from its equally facile binding in a parallel/antiparallel fashion ( II ) with the complementary nucleic acid sequences. These limitations are being systematically addressed with rationally modified PNA analogues. , The solubility of PNAs was improved through conjugation with cationic ligands such as polyamines, lysine 3 at the N/C terminus of the PNA, or guanidinium in backbone without compromising the hydrogen-bonding specificity. The cell penetrability has been improved by conjugation with various transfer molecules such as cell-penetrating peptides .…”

Section: Introductionmentioning

confidence: 99%

“…Consequently, formation of PNA:DNA/RNA complexes is accompanied by conformational changes in PNA to gain enthalpic advantage by hydrogen-bonding and base-stacking interactions accompanied by an undesirable decrease in entropy . Any further increase in the conformational freedom in aeg- PNA through extended backbone , or side-chain structures lead to substantial reduction in the stability of the resulting PNA:DNA/RNA complexes.…”

Section: Introductionmentioning

confidence: 99%

Conformationally Constrained PNA Analogues: Structural Evolution toward DNA/RNA Binding Selectivity

2005

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Since its discovery 12 years ago, aminoethylglycyl peptide nucleic acid (aeg-PNA) has emerged as one of the successful DNA mimics for potential therapeutic and diagnostic applications. An important requisite for in vivo applications that has received inadequate attention is engineering PNA analogues for able discrimination between DNA and RNA as binding targets. Our approach toward this aim is based on structural preorganization of the backbone to hybridization-competent conformations to impart binding selectivity. This strategy has allowed us to design locked PNAs to achieve specific hybridization with DNA or RNA with aims to increase the binding strength without losing the binding specificity. This Account presents results of our rationale in design of different conformationally constrained PNA analogues, their synthesis, and evaluation of hybridization specificities.

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“…As antisense compounds, it finds application in gene silencing therapy and diagnostics Jordan et al (1997) T A B L E 1 (Continued) Kumar and Ganesh (2005) 27 (2R, RS)-A stabilized DNA and RNA complexes while (2S,4S)-T destabilized the DNA or RNA complexes Kumar (2002) 28 It showed the effect of ring size of six-membered cyclic β-aminoacid on the hybridization of pyrrolidinyl PNA to DNA/RNA Aromatic PNA…”

Section: Sl No Name and Structure Usefulness Referencesmentioning

confidence: 99%

Evolution of peptide nucleic acid with modifications of its backbone and application in biotechnology

Das

Pradhan

2020

Chem Biol Drug Des

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Peptide nucleic acids (PNAs) are getting prodigious interest currently in the biomedical and diagnostic field as an extremely powerful tool because of their potentiality to hybridize with natural nucleic acids. Although PNA has strong affinity and sequence specificity to DNA/RNA, there is a considerable ongoing effort to further enhance their special chemical and biological properties for potential application in numerous fields, notably in the field of therapeutics. The toolbox for backbone modified PNAs synthesis has been extended substantially in recent decades, providing a more efficient synthesis of peptides with numerous scaffolds and modifications. This paper reviews the various strategies that have been developed so far for the modification of the PNA backbone, challenging the search for new PNA systems with improved chemical and physical properties lacking in the original aegPNA backbone. The various practical issues and limitations of different PNA systems are also summarized. The focus of this review is on the evolution of PNA by its backbone modification to improve the cellular uptake, sequence specificity, and compatibility of PNA to bind to DNA/RNA. Finally, an insight was also gained into major applications of backbone modified PNAs for the development of biosensors.

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Structural Preorganization of Peptide Nucleic Acids: Chiral Cationic Analogues with Five- or Six-Membered Ring Structures

Cited by 64 publications

References 56 publications

Charge dependent behavior of PNA/DNA/PNA triplexes in the gas phase

Charge dependent behavior of PNA/DNA/PNA triplexes in the gas phase

Conformationally Constrained PNA Analogues: Structural Evolution toward DNA/RNA Binding Selectivity

Evolution of peptide nucleic acid with modifications of its backbone and application in biotechnology

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