Efficacy and Safety of K-877 (Pemafibrate), a Selective PPARα Modulator, in European Patients on Statin Therapy.

Objective: High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG levels through peroxisome proliferator-activated receptor α (PPARα) agonism. Currently available fibrates, however, have relatively low selectivity for PPARα.

Effects of 5-substituted pyrimidine nucleoside bases of WNA on stability of triplex DNA.

Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules, but their recognizable duplexes are limited to homopurine:homopyrimidine sequences by interruption of pyrimidine bases in the purine strand. Despite numerous studies, this problem has not been generally solved. We have recently demonstrated that the new nucleoside analogues, WNA-betaT and WNA-betaC exhibit selective stabilization of the triplexes at a TA and a CG interrupting site, respectively.

Effects of halogenated WNA derivatives on sequence dependency for expansion of recognition sequences in non-natural-type triplexes.

Triplex-forming oligonucleotides (TFOs) are sequence-specific DNA-binding agents, but their target duplexes are limited to homopurine/homopyrimidine sequences because of interruption of the pyrimidines bases in the purine region. This problem has not been fully solved despite a wide variety of studies. Recently, we have developed a bicyclic system as a novel scaffold for nucleoside analogues (WNA, W-shaped nucleoside analogues) and determined two useful compounds, WNA-betaT (2) and WNA-betaC (5), for highly stable and selective triplex formation at a TA and a CG interrupting site, respectively.

Expansion of triplex recognition codes by the use of novel bicyclic nucleoside derivatives (WNA).

Recently, we have developed new base analogs (WNA) and demonstrated that WNA-[see text];T with thymine and WNA-[see text];C with cytosine stabilize n on-natural antiparallel triplexes with a TA or CG interrupting site, respectively. However, limitations in recognizable sequences with the WNA-containing TFO were also found. The objective of this study is to search better WNA analogs for expansion of triplex recognition codes to general duplex sequences.

Selective formation of stable triplexes including a TA or a CG interrupting site with new bicyclic nucleoside analogues (WNA).

Triplex-forming oligonucleotides (TFOs) are potential DNA-targeting molecules and would become powerful tools for genomic research. As the stabilization of the TFO is partially provided by hydrogen bonds to purine bases, the most stable triplexes form with homopurine/homopyrimidine sequences, and a pyrimidine base in the purine strand of the duplex interrupts triplex formation. If a TFO can recognize sequences including such an interrupting site, the target regions in the genome would be expanded to a greater extent.

Design and evaluation of novel nucleoside analogs (WNA) for specific formation of non-natural type triplexes containing a TA or CG interrupting site.

In a search of suitable recognition molecules for the formation of stable non-natural triplex DNA, we have developed the new nucleoside analogs (WNA, W-shape nucleoside analog) bearing an aromatic ring, a recognition base and a bicyclic skeleton to hold them. A successful result with WNA-betaT that recognizes a TA base pair selectively has suggested that the basic structure of the WNA is useful as a scaffold for search of other candidates for the formation of triplex containing a TA or a CG interrupting site. In this study, we have synthesized and investigated binding property of a variety of WNA candidates.

Selective formation of non-natural type triplexes containing TA interrupting sites with the TFO incorporating W-shape nucleic acid (WNA) analogs.

Novel nucleoside analogs have been desired for selective formation of non-natural type triplexes containing TA or CG interrupting sites. We have previously reported that the W-shaped nucleic acid (WNA) would be a useful skeleton to develop new base analog for the formation of non-natural triplexes of antiparallel motif. In this study, we have found that triplex forming oligonucleotide (TFO) incorporating the new WNA analog, WNA-beta T, formed more stable triplex than natural triplex with high selectivity to the TA site.