Ultrasound Molecular Imaging with Targeted Microbubbles for Cancer Diagnostics: From Bench to Bedside

Background

Ultrasound plays an important role in cancer diagnosis. B-mode imaging and contrast-enhanced ultrasound are routinely used to detect cancerous lesions in breast and liver. The use of ultrasound contrast agents (UCAs) such as microbubbles (MBs), which can be functionalized with targeting ligands, has further enabled ultrasound molecular imaging (USMI) of specific molecular markers in pre-clinical and the first clinical studies. As targeted MBs have a diameter of 1–4 μm, they are limited to the blood vasculature upon intravenous injection, and can bind to markers of the vascular endothelium. USMI with targeted MBs was applied for imaging of markers of inflammation, angiogenesis, and the tumor endothelium.

A genetically selected cyclic peptide inhibitor of BCL6 homodimerization

We report an inhibitor of the homodimeric protein-protein interaction of the BCL6 oncoprotein, identified from a genetically encoded SICLOPPS library of 3.2 million cyclic hexapeptides in combination with a bacterial reverse two-hybrid system. This cyclic peptide is shown to bind the BTB domain of BCL6, disrupts its homodimerization, and subsequent binding of the SMRT2 corepressor peptide.     

Reactive group-embedded affinity labeling reagent for efficient intracellular protein labeling

Affinity labeling of a target protein is a powerful method for chemical biology studies. However, it is still difficult to label intracellular proteins efficiently in living cells. We propose the novel design strategy of a reactive group-embedded affinity labeling reagent for efficient protein labeling. With FKBP12 as the model target protein, the ligand binding pocket-oriented labeling reagent could label intracellular protein, whereas protein surface-oriented reagent was ineffective for labeling in living cells, partially because of the intracellular protein fluctuation under the macromolecular crowding effects. These results provide new insight for efficient intracellular protein labeling.     

Thioether-stapled macrocyclic inhibitors of the EH domain of EHD1

Recycling of receptors from the endosomal recycling compartment to the plasma membrane is a critical cellular process, and recycling is particularly important for maintaining invasiveness in solid tumors. In this work, we continue our efforts to inhibit EHD1, a critical adaptor protein involved in receptor recycling. We applied a diversity-oriented macrocyclization approach to produce cyclic peptides with varied conformations, but that each contain a motif that binds to the EH domain of EHD1. Screening these uncovered several new inhibitors for EHD1’s EH domain, the most potent of which bound with a K_d of 3.1 μM. Several of the most potent inhibitors were tested in a cellular assay that measures extent of vesicle recycling. Inhibiting EHD1 could potentially slow cancer invasiveness and metastasis, and these cyclic peptides represent the most potent inhibitors of EHD1 to date.     

The start of a human life program

正The genetic information of a human being is encoded in the genomic DNA of about 3 billion base pairs.Every new individual starts from a one-cell zygote,or called fertilized egg,carrying genetic and epigenetic information from the parents.The developmental process from one single cell to a whole organism depends on the differential regulation of the genetic information encoded     

Discovery of covalent enzyme inhibitors using virtual docking of covalent fragments

Here we present a virtual docking screen of 1648 commercially available covalent fragments, and identified covalent inhibitors of cysteine protease cathepsin L. These inhibitors did not inhibit closely related protease cathepsin B. Thus, we have established virtual docking of covalent fragments as an approach to discover covalent enzyme inhibitors.     

Disruptor of telomeric silencing 1-like (DOT1L) is involved in breast cancer metastasis via transcriptional regulation of MALAT1 and ZEB2

<正>Epigenetics refers to how chromatin-associated factors and reversible chromatin modifications maintain DNA-based programs by regulating the chromatin structure (Strahl and Allis,2000).In recent years,genome sequencing studies of cancer have shown that genes encoding epigenetic factors are commonly mutated in cancer(Garraway and Lander,2013).Dys regulated,or mutant,epigenetic factors influence tumorigenesis progression (Dawson and Kouzarides,     

The Genome of Opium Poppy Reveals Evolutionary History of Morphinan Pathway

正Plants, as primary producers, have been playing an indispensable role in other organisms’ survival and the balance of whole ecosystem on Earth. Especially, they provide the main source of energy, food, and medicine for human beings, some of which are derived from the primary or secondary metabolites