A zymogen-like factor Xa variant corrects the coagulation defect in hemophilia

This paper discusses a therapeutic method to induce coagulation for hemophiliacs. To do this, the authors modified the coagulation factor Xa (FXa) to have decreased sensitivity towards plasma inhibitors. Using the I16L and V17A FXa mutants, blood loss was minimized in hemophilic mouse models to that of wild-type FXa. Additionally, the mutant FXa was compared to current hemophilia treatment, which uses FVIIa. The coagulant properties were shown to be better using the FXa mutant. I thought this paper was interesting because it shows how a simple mutation can have profound medical effects.

Investigating the Antimalarial Action of 1,2,4-Trioxolanes with Fluorescent Chemical Probes

1,2,4-Trioxolane analogs are a class of important antimalarial drugs. There is a need for new anti malaria drugs that are affordable and reliably available. Some peroxide compounds, that contain a sterically hindered 1,2,4-trioxolane ring are currently in clinical trials. The mechanism of action of these peroxide compounds has not been elucidated yet and rises some debate. In order to study the intracellular reactivity of 1,2,4-trioxolanes and the mechanism of fragmentation of the peroxide bond when it reacts with Ferrous Iron, they designed fluorescent probes. The fluorescent probes were synthesized by substituting their lead compound with a dansyl group. They found that the trioxolane ring fragments within parasites and that fragmentation results in accumulation of adamantane fragments in neutral lipid bodies.

Network analysis of microRNAs and their regulation in human ovarian cancer

This paper introduces the network of mircoRNAs and regulatory transcription factors (TF) that are associated in ovarian cancer (OC) development. The network is generated from different databases searching for interactions of all miRNAs, TFs, and TcoFs related to OC. From the combined interactions they were able to identify the component s that had the most influence to the network. By studying the network of miRNAs and their regulations expands our knowledge of molecular mechanism in OC development. 

T he proteoglycan bikunin has a defined sequence

This paper shows that proteoglycans are likely composed of specific sequences of glycans by sequencing the proteoglycan bikunin. To sequence bikunin, tandem MS was used in addition to PAGE gels. The authors discovered that odd numbered chains exist in greater abundance and a sulfated and non-sulfated sequence exist within the bikunin sequence. I thought this was an interesting paper because previously proteoglycan sequences were thought to be random, which rarely occurs in biological systems. Ly et al. provide evidence that this is probably not the case and that proteoglycans likely have a defined sequence.

Photoactivatable Caged Cyclic RGD Peptide for Triggering Integrin Binding and Cell Adhesion to Surfaces

This ChemBioChem paper uses an immobilized photocaged peptide to photochemically control cell adhesion. The authors also show that the amount and location of cells could be controlled. This could be a new technology in tissue engineering or cell biology.

The Curious Chemical Biology of Cytosine: Deamination, Methylation,and Oxidation as Modulators of Genomic Potential

This paper from ACS Chemical Biology describes the many roles that cytosine modification has for biological function. The cytosine "wild card" terminology comes from the different potential of each state of cytosine, suggesting it has a much larger role in genetic regulation than purely being a coding base. Anyone interested in DNA/RNA modifications should take a look a this review, as it encompasses a diverse set of cytosine chemical alterations.

Small molecule inhibition of RISC loading

In this paper, Kiriakidou’s lab establish a tool using fluorescence polarization of TAMRA-labeled small RNA to identify new compounds that inhibit the miRNA loading to Ago2 protein which is a crucial step in the RNA interference pathway. I found this paper interesting because the discovery of the miRNA and Ago protein binding will bring better understanding of function of the Ago protein as well as the the RNA interference pathway.

Chemical Approaches To Understand the Language of Histone Modifications

In class we talked about using unnatural amino acid mutagenesis to site-specifically modify histones. This review article talks about that method as well as several others. Solid-phase peptide synthesis can be used to create relatively short pieces of histones with the proper modifications. This technique is great for high-throughput screening with proteins thought to bind histones. The problem is that some of the interactions may be context-specific. Native chemical ligation (NCL) can be used to join peptides together, but length is still a factor. Expressed protein ligation (EPL) is a similar technique in which recombinant proteins can be cleaved and joined to synthetic peptides. The next step is to study the effects of multiple different modifications on the same nucleosome, as well as the effects of asymmetric modification of neighboring nucleosomes.

Bacteriophages and Viruses as a Support for Organic Synthesis and Combinatorial Chemistry

We learned about DNA-encoded small molecules. This is a review article that starts with that idea, but makes the DNA "encoding" in a "living" organism, as oppsed to attaching the small molecule to the DNA itself. Since you can't really encode a small molecule in DNA, but rather have a sequence-specific tag for your unique molecule, the DNA doesn't even have to encode a functional protein, like i showed with the phage display on tuesday. Combinatorial chemistry seeks to produce huge variants of chemicals and there is probably an equally huge possibility for DNA sequences...Now how to track each one...and think of selections for your chemistry, and amplify your 'barcode'.

Toward Targeting RNA Structure: Branched Peptides as Cell-Permeable Ligands to TAR RNA

We had a seminar speaker visit us recently who discussed designing branched peptide ligands for targeting RNA. This recently published paper from Webster Santos describes that work in more detail for those who were interested in his talk. Though he pushed the boronation of these molecules as a selling point, it is interestingly not mentioned in this paper - way have been a way to get "chemists" interested in a biological application.