Protein-structure studies helped demonstrate that the primary target of antibody-based COVID-19 immunity is the part of the virus’s spike protein that can most easily mutate. The work anticipated the rise of SARS-CoV-2 variants and guides the selection of antibody therapeutics that are likely to be more resistant to immune escape. Read more »
Single-Domain Multiferroic Array-Addressable Terfenol-D (SMArT) Micromagnets for Programmable Single-Cell Capture and Release
Researchers develop programmable multiferroic micromotors that enable single-cell manipulation based on time-dependent functions of individual cells, such as cell secretion. Smart programmable multiferroic materials lay the groundwork for large-scale automated single-cell sorting and enable a broad spectrum of biotechnology applications. Read more »
Programmable Micromagnets for Single-Cell Sorting
Researchers demonstrated that electrically induced mechanical strain can control the magnetic state of tiny magnets used to sort biological cells. The work lays the foundation for a programmable, single-cell sorting platform to support a wide variety of biotechnology applications, including personalized cancer treatments. Read more »
How X-Rays Could Make Reliable, Rapid COVID-19 Tests a Reality
A highly sensitive lateral flow assay—the same type of device used in home pregnancy tests—could be developed using pairs of rigid antibodies that bind to the SARS-CoV-2 nucleocapsid protein. SAXS data showed that a particular pair of monoclonal antibodies bound to the nucleocapsid protein very strongly and stably, in part due to the antibodies’ rigidity. Read more »
Structure-Based Design of Selective LONP1 Inhibitors for Probing In Vitro Biology
LONP1 is an AAA+ protease that maintains mitochondrial homeostasis by removing damaged or misfolded proteins. Elevated activity and expression promotes cancer cell proliferation and resistance to apoptosis-inducing reagents. Herein, we report the development of selective boronic acid-based LONP1 inhibitors using structure-based drug design as well as the first structures of human LONP1 bound to various inhibitors. Read more »
Targeting KRAS Mutant Cancers via Combination Treatment: Discovery of a 5-Fluoro-4-(3H)-quinazolinone Aryl Urea pan-RAF Kinase Inhibitor
The cover feature shows a chessboard (representative of KRAS mutant cells) and how the concerted action of the MEK inhibitor cobimetinib (rook) and the new selective pan-RAF inhibitor GNE-0749 (queen) force the opposing king (phospho-ERK, the downstream signaling node of RAF and MEK) into checkmate. Read more »
Mystery Protein Helps COVID–19 Avoid Immunity
Using the Advanced Light Source (ALS), researchers solved the structure of ORF8, a protein specific to SARS-CoV-2. Understanding the structure of ORF8 opens the door to therapy studies targeting SARS-CoV-2, the virus responsible for causing COVID-19. Read more »
3D Whole-Cell Mapping of Insulin Secretion
Researchers used soft x-ray tomography to gain a 3D whole-cell view of how insulin-producing pancreatic cells react upon exposure to glucose and a diabetes drug. The approach enables direct quantification of intracellular responses before, during, and after cell stimulation, providing new insights into how drugs alter cell function. Read more »
Construction, characterization and crystal structure of a fluorescent single-chain Fv chimera
In vitro display technologies based on phage and yeast have a successful history of selecting single-chain variable fragment (scFv) antibodies against various targets. However, single-chain antibodies are often unstable and poorly expressed. We explore the feasibility of converting scFv antibodies to an intrinsically fluorescent format by inserting a monomeric, stable fluorescent protein between the light- and heavy-chain variable regions. Read more »
CC-90009, a novel cereblon E3 ligase modulator, targets acute myeloid leukemia blasts and leukemia stem cells
A number of clinically validated drugs have been developed by repurposing the CUL4-DDB1-CRBN-RBX1 (CRL4CRBN) E3 ubiquitin ligase complex with molecular glue degraders to eliminate disease-driving proteins. Here, we present the identification of a first-in-class GSPT1-selective cereblon E3 ligase modulator, CC-90009, that targets acute myeloid leukemia blasts and leukemia stem cells. Read more »
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