65953-56-2Relevant articles and documents
Strategy and validation of a structure-based method for the discovery of selective inhibitors of PAK isoforms and the evaluation of their anti-cancer activity
Song, Pei-Lu,Wang, Gang,Su, Yuan,Wang, Han-Xun,Wang, Jian,Li, Feng,Cheng, Mao-Sheng
, (2019/08/12)
p21 activated kinase 4 (PAK4), which belongs to the serine/threonine (Ser/Thr) protein kinase family, is a representative member of the PAK family and plays a significant role in multiple processes associated with cancer development. In this study, structure-based virtual screening was performed to discover novel and selective small molecule scaffolds, and a 6-hydroxy-2-mercapto-3-phenylpyrimidin-4(3H)-one-based compound (SPU-106, 14No.) was identified as an effective PAK4 inhibitor. By combining both a molecular docking study and molecular dynamics (MD) simulation strategies, the binding mode was determined in the PAK4 site. The SPU-106 compound could efficiently and selectively bind to the PAK4 kinase domain at an IC50 of 21.36 μM according to the kinase analysis. The designed molecular probe demonstrated that SPU-106 binds to the kinase domain in the C-terminus of PAK4. Further investigation revealed that the SPU-106 had a strong inhibitory effect on the invasion of SGC7901 cells but without any cytotoxicity. The western blot analysis indicated that the compound potently inhibited the PAK4/LIMK1/cofilin and PAK4/SCG10 signaling pathways. Thus, our work shows the successful application of computational strategies for the discovery of selective hits, and SPU-106 may be an effective PAK4 inhibitor for further development as an antitumor agent.
Biomolecule-compatible, highly branched polymer and biomolecular-recognition surface
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Page/Page column 15, (2016/04/05)
A biomolecule-compatible highly branched polymer obtained by polymerizing a monomer having an alkylene oxide and two or more radically polymerizable double bonds in a molecule in presence of a polymerization initiator in 5 mol % or more and 200 mol % or less relative to the moles of monomer, wherein molecular terminals of biomolecule-compatible highly branched polymer have one biomolecular site of at least one pair from the group of combination pairs of biotin and avidin, an antigen and antibody, polynucleotide and polynucleotide having complementary base sequence thereof, cDNA and mRNA, enzyme and substrate, an enzyme and product, an enzyme and competitive inhibitor, an enzyme (binding site) and coenzyme, an enzyme (binding site) and triazine dye, protease and protease inhibitor, Fc site and protein A, Fc site and protein G, lectin and sugar, hormone receptor and hormone, DNA and DNA binding protein, heparin and fibronectin, and heparin and laminin.
Photocleavable ligands for protein decoration of DNA nanostructures
Brglez, Josipa,Ahmed, Ishtiaq,Niemeyer, Christof M.
, p. 5102 - 5104 (2015/05/13)
This work describes the synthesis of amino-reactive, photocleavable hapten-modifiers and their application as affinity tags for DNA nanostructures. In particular, N-hydroxysuccinimide-activated linkers containing an α-methyl-nitroveratryl-butyric acid group and carboxyfluorescein or biotin were synthesized and coupled to alkyl-amino-modified DNA oligonucleotides. The resulting conjugates were then incorporated into DNA origami nanostructures. As demonstrated by electrophoresis and AFM imaging, the functionalized nanostructures were capable to bind cognate proteins which could then be cleaved-off by irradiation. Owing to its modularity, this approach to control protein binding should be useful for a wide variety of functional DNA nanostructures.
