Glycosylation: Rising Potential for Prostate Cancer Evaluation

Prostate cancer is the second most commonly diagnosed cancer among men. Alterations in protein glycosylation are confirmed to be a reliable hallmark of cancer. Prostate-specific antigen is the biomarker that is used most frequently for prostate cancer detection, although its lack of sensitivity and specificity results in many unnecessary biopsies. A wide range of glycosylation alterations in prostate cancer cells, including increased sialylation and fucosylation, can modify protein function and play a crucial role in many important biological processes in cancer, including cell signalling, adhesion, migration, and cellular metabolism. In this review, we summarize studies evaluating the prostate cancer associated glycosylation related alterations in sialylation, mainly α2,3-sialylation, core fucosylation, branched N-glycans, LacdiNAc group and presence of truncated O-glycans (sTn, sT antigen). Finally, we discuss the great potential to make use of glycans as diagnostic and prognostic biomarkers for prostate cancer.

Implementation of adaptive integration method for free energy calculations in molecular systems

Estimating free energy differences by computer simulation is useful for a wide variety of applications such as virtual screening for drug design and for understanding how amino acid mutations modify protein interactions. However, calculating free energy differences remains challenging and often requires extensive trial and error and very long simulation times in order to achieve converged results. Here, we present an implementation of the adaptive integration method (AIM). We tested our implementation on two molecular systems and compared results from AIM to those from a suite of other methods. The model systems tested here include calculating the solvation free energy of methane, and the free energy of mutating the peptide GAG to GVG. We show that AIM is more efficient than other tested methods for these systems, that is, AIM results converge to a higher level of accuracy and precision for a given simulation time.

Antisense Oligonucleotides: Pharmacology and Delivery Strategies

Antisense oligonucleotide therapy is a dominant drug discovery approach that can explicitly modify protein synthesis through numerous mechanisms. The limitations of antisense oligonucleotide (ASO) therapy in delivery strategies have been overcome in recent years with different ligands carriers, as well as, through nanocarriers. ASO therapy was successfully applied towards targeting a wide range of therapeutic areas. There is an expanding enthusiasm in extending the utilization of antisense compounds to numerous different diseases due to their safe and potential therapeutic outcomes. Thus, the present review attempted to elaborate on the fundamental idea of antisense technology, approaches, and safe and effective delivery methods.

Click chemistry-based imaging to study the tissue distribution of the curcumin–protein complex in mice

Using click chemistry-based fluorescence imaging, here we show that curcumin, a bioactive dietary compound with a thiol-reactive α,β-unsaturated carbonyl moiety, can covalently modify protein thiols in colon and liver tissues in mice.

Sulfur: the heart of nitric oxide-dependent redox signalling

Nitric oxide (NO), more benign than its more reactive and damaging related molecules, reactive oxygen species (ROS), is perfectly suited for duties as a redox signalling molecule. A key route for NO bioactivity is through S-nitrosation, the addition of an NO moiety to a protein Cys thiol (-SH). This redox-based, post-translational modification (PTM) can modify protein function analogous to more well established PTMs such as phosphorylation, for example by modulating enzyme activity, localization, or protein–protein interactions. At the heart of the underpinning chemistry associated with this PTM is sulfur. The emerging evidence suggests that S-nitrosation is integral to a myriad of plant biological processes embedded in both development and environmental relations. However, a role for S-nitrosation is perhaps most well established in plant–pathogen interactions.

A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity

A unique peptide stabilization method provides a tethered sulfonium that can rapidly and selectively modify protein cysteine in close vicinity.

Osmolytes modify protein dynamics and function of tetrameric lactate dehydrogenase upon pressurization

We present a study of the combined effects of natural cosolvents (TMAO, glycine, urea) and pressure on the activity of the tetrameric enzyme lactate dehydrogenase (LDH).