Origin and evolution of exon/intron junctions

In nuclear mRNA genes, exon/intron junctions (both exon/intron and intron/exon junctions in this paper) possess the specific duplex pattern with the corresponding ends (3′ to 3′, 5′ to 5′) of exons and introns more or less identical. In genes with group I or group II introns, overall analyses indicate there are also related patterns in their exon/intron junctions. From the analysis of these specific regions of split genes and the study of the composition of primitive genomes, it is proposed that the sequences of primitive exons and introns are identical at least in their corresponding boundary regions. And more fundamentally, it may be concluded that exon/intron junctions were originally related to tandem repeated sequences in the earliest genomes. Results from a preliminary analysis of specific motifs in modern repeated sequences support such a view on the origin of exon/intron junctions. As for the evolution of exon/intron junctions, there have been multiple rather than single paths.     

Design of new bidentate ligands constructed of two Hoechst 33258 units for discrimination of the length of two A3T3 binding motifs

[structure: see text] The aim of this study is to develop bidentate minor-groove binders that bind the double binding motifs cooperatively. The new bidentate ligands (1) have been designed by connecting two Hoechst 33258 units with a polyether linker for cooperative binding with two remote A3T3 sites of DNA. The linker is introduced to the benzimidazole ring so that it is located at the convex side of the Hoechst unit. DNA binding affinity of the ligands was evaluated by measuring surface plasmon resonance (SPR), circular dichroism, and fluorescence spectra. Interestingly, the bidentate ligands (1) did not show affinity to DNA1 with a single A3T3 motif but showed selective affinity to DNA2 with two A3T3 motifs. The Long Bis-H (1L) having a long polyether linker showed specific binding to DNA2(6) with two A3T3 motifs separated by six nonbinding base pairs. The Long Bis-H (1L) has also shown specific binding to the three-way junction DNA4 with two A3T3 motifs. This study has demonstrated that DNA with double binding motifs can be selectively recognized by the newly designed bidentate ligands.     

Selection of a synthetic glycan oligomer from a library of DNA-templated fragments against DC-SIGN and inhibition of HIV gp120 binding to dendritic cells

We report the synthesis of a nucleic acid-encoded carbohydrate library, its combinatorial self-assembly into 37,485 pairs and a screen against DC-SIGN leading to the identification of consensus ligand motifs. A prototypical example from the selected pairs was shown to have enhanced binding. A dendrimer incorporating the selected motifs inhibited gp120's binding to dendritic cells with higher efficiency than mannan.