Steady State and Time-Dependent Fluorescent Peptide Assays for Protein Kinases.

Protein kinases catalyze the phosphorylation of proteins most commonly on Ser, Thr, and Tyr residues and regulate many cellular events in eukaryotic cells, such as cell cycle progression, transcription, metabolism, and apoptosis. Protein kinases each have a conserved ATP-binding site and one or more substrate-binding site(s) that exhibit recognition features for different protein substrates. By bringing ATP and a substrate into proximity, each protein kinase can transfer the γ phosphate of the ATP molecule to a hydroxyl group of the target residue on the substrate.

Unleashing the Potential of 1,3-Diketone Analogues as Selective LH2 Inhibitors.

Lysyl hydroxylase 2 (LH2) catalyzes the formation of highly stable hydroxylysine aldehyde-derived collagen cross-links (HLCCs), thus promoting lung cancer metastasis through its capacity to modulate specific types of collagen cross-links within the tumor stroma. Using and from our previous high-throughput screening (HTS) as lead probes, we prepared a series of 1,3-diketone analogues, -, and identified and that inhibit LH2 with IC's of approximately 300 and 500 nM, respectively. Compounds and demonstrate selectivity for LH2 over LH1 and LH3.