Nickel-Catalyzed Deoxygenative Amidation of Alcohols with Carbamoyl Chlorides

We report a deoxygenative amidation reaction of alcohols with carbamoyl chlorides to afford amides through nickel–photoredox dual catalysis. Good to excellent yields can be obtained even for diverse complex sugar and steroid derivatives. The reaction is scalable, and the synthetic utility of the reaction was demonstrated by the homologation of alcohols to deliver several important γ-amino alcohols and a synthetically challenging bioactive compound intermediate

Presentation2_Ubiquitous conservative interaction patterns between post-spliced introns and their mRNAs revealed by genome-wide interspecies comparison.pdf

Introns, as important vectors of biological functions, can influence many stages of mRNA metabolism. However, in recent research, post-spliced introns are rarely considered. In this study, the optimal matched regions between introns and their mRNAs in nine model organism genomes were investigated with improved Smith–Waterman local alignment software. Our results showed that the distributions of mRNA optimal matched frequencies were highly consistent or universal. There are optimal matched frequency peaks in the UTR regions, which are obvious, especially in the 3′-UTR. The matched frequencies are relatively low in the CDS regions of the mRNA. The distributions of the optimal matched frequencies around the functional sites are also remarkably changed. The centers of the GC content distributions for different sequences are different. The matched rate distributions are highly consistent and are located mainly between 60% and 80%. The most probable value of the optimal matched segments is about 20 bp for lower eukaryotes and 30 bp for higher eukaryotes. These results show that there are abundant functional units in the introns, and these functional units are correlated structurally with all kinds of sequences of mRNA. The interaction between the post-spliced introns and their corresponding mRNAs may play a key role in gene expression.</p

Enhanced Binding Affinity for an i‑Motif DNA Substrate Exhibited by a Protein Containing Nucleobase Amino Acids

Several variants of a nucleic acid binding motif (RRM1) of putative transcription factor hnRNP LL containing nucleobase amino acids at specific positions have been prepared and used to study binding affinity for the <i>BCL2</i> i-motif DNA. Molecular modeling suggested a number of amino acids in RRM1 likely to be involved in interaction with the i-motif DNA, and His24 and Arg26 were chosen for modification based on their potential ability to interact with G14 of the i-motif DNA. Four nucleobase amino acids were introduced into RRM1 at one or both of positions 24 and 26. The introduction of cytosine nucleobase <b>2</b> into position 24 of RRM1 increased the affinity of the modified protein for the i-motif DNA, consistent with the possible Watson–Crick interaction of <b>2</b> and G14. In comparison, the introduction of uracil nucleobase <b>3</b> had a minimal effect on DNA affinity. Two structurally simplified nucleobase analogues (<b>1</b> and <b>4</b>) lacking both the N-1 and the 2-oxo substituents were also introduced in lieu of His24. Again, the RRM1 analogue containing <b>1</b> exhibited enhanced affinity for the i-motif DNA, while the protein analogue containing <b>4</b> bound less tightly to the DNA substrate. Finally, the modified protein containing <b>1</b> in lieu of Arg26 also bound to the i-motif DNA more strongly than the wild-type protein, but a protein containing <b>1</b> both at positions 24 and 26 bound to the DNA less strongly than wild type. The results support the idea of using nucleobase amino acids as protein constituents for controlling and enhancing DNA–protein interaction. Finally, modification of the i-motif DNA at G14 diminished RRM1–DNA interaction, as well as the ability of nucleobase amino acid <b>1</b> to stabilize RRM1–DNA interaction

Presentation3_Ubiquitous conservative interaction patterns between post-spliced introns and their mRNAs revealed by genome-wide interspecies comparison.pdf

Introns, as important vectors of biological functions, can influence many stages of mRNA metabolism. However, in recent research, post-spliced introns are rarely considered. In this study, the optimal matched regions between introns and their mRNAs in nine model organism genomes were investigated with improved Smith–Waterman local alignment software. Our results showed that the distributions of mRNA optimal matched frequencies were highly consistent or universal. There are optimal matched frequency peaks in the UTR regions, which are obvious, especially in the 3′-UTR. The matched frequencies are relatively low in the CDS regions of the mRNA. The distributions of the optimal matched frequencies around the functional sites are also remarkably changed. The centers of the GC content distributions for different sequences are different. The matched rate distributions are highly consistent and are located mainly between 60% and 80%. The most probable value of the optimal matched segments is about 20 bp for lower eukaryotes and 30 bp for higher eukaryotes. These results show that there are abundant functional units in the introns, and these functional units are correlated structurally with all kinds of sequences of mRNA. The interaction between the post-spliced introns and their corresponding mRNAs may play a key role in gene expression.</p

Presentation1_Ubiquitous conservative interaction patterns between post-spliced introns and their mRNAs revealed by genome-wide interspecies comparison.zip

Introns, as important vectors of biological functions, can influence many stages of mRNA metabolism. However, in recent research, post-spliced introns are rarely considered. In this study, the optimal matched regions between introns and their mRNAs in nine model organism genomes were investigated with improved Smith–Waterman local alignment software. Our results showed that the distributions of mRNA optimal matched frequencies were highly consistent or universal. There are optimal matched frequency peaks in the UTR regions, which are obvious, especially in the 3′-UTR. The matched frequencies are relatively low in the CDS regions of the mRNA. The distributions of the optimal matched frequencies around the functional sites are also remarkably changed. The centers of the GC content distributions for different sequences are different. The matched rate distributions are highly consistent and are located mainly between 60% and 80%. The most probable value of the optimal matched segments is about 20 bp for lower eukaryotes and 30 bp for higher eukaryotes. These results show that there are abundant functional units in the introns, and these functional units are correlated structurally with all kinds of sequences of mRNA. The interaction between the post-spliced introns and their corresponding mRNAs may play a key role in gene expression.</p