Peptide nucleic acid or PNA is a synthetic DNA mimic that contains a sequence of nucleobases attached to a peptide-like backbone derived from N-2-aminoethylglycine. The semi-rigid PNA backbone acts as a scaffold that arranges the nucleobases in a proper orientation and spacing so that they can pair with their complementary bases on another DNA, RNA, or even PNA strand perfectly well through the standard Watson–Crick base-pairing. The electrostatically neutral backbone of PNA contributes to its many unique properties that make PNA an outstanding member of the xeno-nucleic acid family. Not only PNA can recognize its complementary nucleic acid strand with high affinity, but it does so with excellent specificity that surpasses the specificity of natural nucleic acids and their analogs. Nevertheless, there is still room for further improvements of the original PNA in terms of stability and specificity of base-pairing, direction of binding, and selectivity for different types of nucleic acids, among others. This review focuses on attempts towards the rational design of new generation PNAs with superior performance by introducing conformational constraints such as a ring or a chiral substituent in the PNA backbone. A large collection of conformationally rigid PNAs developed during the past three decades are analyzed and compared in terms of molecular design and properties in relation to structural data if available. Applications of selected modified PNA in various areas such as targeting of structured nucleic acid targets, supramolecular scaffold, biosensing and bioimaging, and gene regulation will be highlighted to demonstrate how the conformation constraint can improve the performance of the PNA. Challenges and future of the research in the area of constrained PNA will also be discussed.

Clitoria ternatea (commonly known as blue pea) flower petal extract (CTE) is used as a natural colorant in a variety of foods and beverages. The objective of study was to determine the inhibitory effect of CTE on adipogenesis in 3T3-L1 preadipocytes. The phytochemical profiles of CTE were analyzed by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Anti-adipogenesis effect of CTE was measured by using Oil Red O staining, intracellular triglyceride assay, quantitative real-time PCR and western blot analysis in 3T3-L1 adipocytes. Cell cycle studies were performed by flow cytometry. Lipolysis experiments were performed using a colorimetric assay kit. In early stages, CTE demonstrated anti-adipogenic effects through inhibition of proliferation and cell cycle retardation by suppressing expression of phospho-Akt and phospho-ERK1/2 signaling pathway. The results also showed that CTE inhibited the late stage of differentiation through diminishing expression of adipogenic transcription factors including PPARγ and C/EBPα. The inhibitory action was subsequently attenuated in downregulation of fatty acid synthase and acetyl-CoA carboxylase, causing the reduction of TG accumulation. In addition, CTE also enhanced catecholamine-induced lipolysis in adipocytes. These results suggest that CTE effectively attenuates adipogenesis by controlling cell cycle progression and downregulating adipogenic gene expression.

Internally pyrene-labeled pyrrolidinyl PNA yields much larger fluorescence increase than terminally labeled PNA upon hybridization with complementary DNA.