Medusa's gaze: Cell traces and fibrils but no collagen in permineralized Jurassic ichthyosaur bone.

Bone is formed by specialized cells whose activity allows bone to grow, change shape, and repair itself. Its composite structure of collagen fibrils and bioapatite nanocrystals gives bone exceptional mechanical strength. Using scanning electron microscopy, we show in fossil ichthyosaurs, 150 to 200 million years old, from the Jurassic of France and the UK, abundant and direct evidence of cellular activity on the fossilized forming, resting, and resorbing surfaces of bone trabeculae, as well as bone fibrils, Sharpey fibers, and cartilage fibers.

Induced cell phenotype activity recording of DNA-tagged ligands.

Based on their ability to canvas vast genetic or chemical space at low cost and high speed, DNA-encoded libraries (DEL) have served to enable both genomic and small molecule discovery. Current DEL chemical library screening approaches focus primarily on target-based affinity or activity. Here we describe an approach to record the phenotype-based activity of DNA-encoded small molecules on their cognate barcode in living cells.

Design, Synthesis, and Biochemical Evaluation of Novel MLK3 Inhibitors: A Target Hopping Example.

The human kinome has tremendous medical potential. In the past decade, mixed-lineage protein kinase 3 (MLK3) has emerged as an interesting and druggable target in oncogenic signaling. The important role of MLK3 has been demonstrated in several types of cancer.

Switching Residues: A Platform for the Synthesis of Fidaxomicin Antibiotics.

Peripheral modification is often the main approach to optimize natural products for improved biological activity or desired physicochemical properties. This procedure inevitably increases molecular weight, often accompanied by undesired increased lipophilicity. Removing structural elements from natural products is not always tolerated.