Previously Published Phosphatase Probes have Limited Utility Due to their Unspecific Reactivity.

This study explores the use of activity-based protein profiling to study protein tyrosine phosphatases. With the discovery of allosteric SHP2 inhibitors, this enzyme family has resurfaced as interesting drug targets. Therefore, we envisioned that previously described direct electrophiles and quinone methide-based traps targeting phosphatases could be applied in competitive activity-based protein profiling assays.

The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2).

Here we present the rational design and synthetic methodologies towards proteolysis-targeting chimeras (PROTACs) for the recently-emerged target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective, brain-penetrating kinase inhibitors were selected, and their structure was appropriately modified to assemble a cereblon-targeting PROTAC. Biological data show strong kinase inhibition and the ability of the synthesized compounds to enter the cells.

PROTACs- a game-changing technology.

: Proteolysis - targeting chimeras (PROTACs) have emerged as a new modality with the potential to revolutionize drug discovery. PROTACs are heterobifunctional molecules comprising of a ligand targeting a protein of interest, a ligand targeting an E3 ligase and a connecting linker. The aim is instead of inhibiting the target to induce its proteasomal degradation.

Spatial and Temporal Distribution of Norovirus and E. coli in Sydney Rock Oysters Following a Sewage Overflow into an Estuary.

This paper reports a study of norovirus (NoV) GII distribution and persistence in Sydney rock oysters (SRO) (Saccostrea glomerata) located in an estuary after a pump station sewage overflow. SRO were strategically placed at six sites spanning the length of the estuary from the pump station to the sea. The spatial and temporal distribution of NoV, hepatitis A virus (HAV) and Escherichia coli (E.

A survey of Australian oysters for the presence of human noroviruses.

Impending international policies for norovirus in oysters and the lack of Australian data suggested there was a need to undertake a national survey of norovirus in oysters. Two geographically distinct oyster-growing areas from each of three Australian states were sampled on 4 occasions during 2010 and 2011. The sites selected were considered by state shellfish authorities to be the most compromised with respect to the potential for human faecal contamination as identified by shoreline surveys.