Quantitative Characterization of Bivalent Probes for a Dual Bromodomain Protein, Transcription Initiation Factor TFIID Subunit 1 was written by Suh, Junghyun L.;Watts, Brian;Stuckey, Jacob I.;Norris-Drouin, Jacqueline L.;Cholensky, Stephanie H.;Dickson, Bradley M.;An, Yi;Mathea, Sebastian;Salah, Eidarus;Knapp, Stefan;Khan, Abid;Adams, Alexander T.;Strahl, Brian D.;Sagum, Cari A.;Bedford, Mark T.;James, Lindsey I.;Kireev, Dmitri B.;Frye, Stephen V.. And the article was included in Biochemistry in 2018.HPLC of Formula: 823-58-5 This article mentions the following:
Multivalent binding is an efficient means to enhance the affinity and specificity of chem. probes targeting multidomain proteins in order to study their function and role in disease. While the theory of multivalent binding is straightforward, phys. and structural characterization of bivalent binding encounters multiple tech. difficulties. We present a case study where a combination of exptl. techniques and computational simulations was used to comprehensively characterize the binding and structure-affinity relationships for a series of Bromosporine-based bivalent bromodomain ligands with a bivalent protein, Transcription Initiation Factor TFIID subunit 1 (TAF1). Exptl. techniques-Isothermal Titration Calorimetry, X-ray Crystallog., CD, Size Exclusion Chromatog.-Multi-Angle Light Scattering, and Surface Plasmon Resonance-were used to determine structures, binding affinities, and kinetics of monovalent ligands and bivalent ligands with varying linker lengths. The exptl. data for monomeric ligands were fed into explicit computational simulations, in which both ligand and protein species were present in a broad range of concentrations, and in up to a 100 s time regime, to match exptl. conditions. These simulations provided accurate estimates for apparent affinities (in good agreement with exptl. data), individual dissociation microconstants and other microscopic details for each type of protein-ligand complex. We conclude that the expected efficiency of bivalent ligands in a cellular context is difficult to estimate by a single technique in vitro, due to higher order associations favored at the concentrations used, and other complicating processes. Rather, a combination of structural, biophys., and computational approaches should be utilized to estimate and characterize multivalent interactions. In the experiment, the researchers used many compounds, for example, 4-Amino-3,6-dichloropyridazine (cas: 823-58-5HPLC of Formula: 823-58-5).
4-Amino-3,6-dichloropyridazine (cas: 823-58-5) belongs to pyridazine derivatives. Pyridazine-based compounds continued to be a great source of biologically active compounds as evidenced by the number of publications which emerged in 2021. The activity depends upon the changes of substituted groups in the pyridazine ring system resulting in different biological activities. In addition, the natural pyrimidine bases uracil, thymine, and cytosine, which are constituents of the nucleic acids, are found to be the most important naturally occurring diazines.HPLC of Formula: 823-58-5
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem