The two subunits of core binding factor (Runx1 and CBFbeta) play critical roles in hematopoiesis and are frequent targets of chromosomal translocations found in leukemia. The binding of the CBFbeta-smooth muscle myosin heavy chain (SMMHC) fusion protein to Runx1 is essential for leukemogenesis, making this a viable target for treatment. We have developed inhibitors with low micromolar affinity which effectively block binding of Runx1 to CBFbeta. NMR-based docking shows that these compounds bind to CBFbeta at a site displaced from the binding interface for Runx1, that is, these compounds function as allosteric inhibitors of this protein-protein interaction, a potentially generalizable approach. Treatment of the human leukemia cell line ME-1 with these compounds shows decreased proliferation, indicating these are good candidates for further development. 相似文献
Tyrosinase/laccase bienzyme biosensor for amperometric determination of phenolic compounds was constructed. Enzymes were immobilized in titania gel matrix. The obtained biosensor was successfully used for determination of 2,6-dimethoxyphenol, 4-tertbutylcatechol, 4-methylcatechol, 3-chlorophenol and catechol. The highest sensitivity and the widest linear range were noticed for catechol, 234 mA L mol− 1 and 2.0 × 10− 7–3.2 × 10− 5 mol/L, respectively. Detection limit for catechol, at signal-to-noise ratio of 3 was 1.3 × 10− 7 mol/L. 相似文献
A new vasopressin analogue, [His(1,6)]AVP, was synthesized and characterized by potentiometric measurements as well as by UV-Vis, CD and EPR spectroscopy. At the physiological pH the peptide forms a stable complex with Cu(2+) ions which is characterized by the {NH(2), N(Im), N(Im(macrochelate))} binding mode. The replacement of both Cys by His residues in the vasopressin sequence results in a very significant increase in the efficiency of Cu(2+) binding. 相似文献
Reactions of Ti(OiPr)4 or Zr(OEt)4 with 4 equivalents of 2,3-dihydro-2,2-dimethyl-7-benzofuranol (ddbfoH) in toluene gave neutral complexes that in the solid state are dimers of [Ti(micro-ddbfo)2(ddbfo)6] and [Zr(ddbfo)3(EtOH)(micro-EtO)]2 composition. The former could also be conveniently synthesized in a direct reaction of TiCl4 with ddbfoH. This air-stable aryloxo compound was found to initiate living ring-opening polymerization of lactides affording polyesters with narrow molecular weight distribution. It also catalyzed addition of terminal acetylenes to aryl aldehydes. 相似文献
The aim of this study was to test selected factors, such as sample preparation and measurement procedure, potentially influencing repeatability of DSC analysis of milk fat melting and crystallization. The study investigated the effect of such factors as scanning rate, type of sample pans, method of butter dehydration, and final temperature in the cooling experiment. Based on recorded results, it was observed that cooling rate has a considerable effect on temperature, enthalpy, and height of peaks in the process of milk fat crystallization, as well as peak height and enthalpy in the melting process. By contrast, in the melting process no significant differences were observed in all measured temperatures in the range of heating rate of 2–20 °C min?1 (p > 0.05). No statistically significant effect on thermodynamic parameters was found for sample pan type, the applied butter dehydration method and various final cooling temperatures (?60, ?50, and ?40 °C) either in the melting or crystallization processes. Only temperature of the second peak (Tc2) in the crystallization process constituted an exception in this respect, with significant differences (p ≤ 0.05) being recorded depending on the applied pan and dehydration method. With regard to the dehydration method, for the extraction and centrifugation methods the first peak forming during crystallization was characterized by high instability, manifested by various peak shape. Generally, it was found that the analysis of the melting and crystallization processes in milk fat, despite its complex composition, is characterized by high repeatability. Mean values of RSD calculated from all the experiments were very low, i.e., 1.8 % for the temperature in the melting process and 1.5 % in crystallization, 0.9 % for melting enthalpy, and 3.2 % for crystallization enthalpy, whereas for peak heights in melting it was 2.9 % and for crystallization it was 9.3 %, respectively. 相似文献
We characterize the family of quotients of peripherally continuous functions. Moreover, we study cardinal invariants related
to quotients in the case of peripherally continuous functions and the complement of this family. 相似文献
Triple duty : A synthetic molecular clip traps nicotinamide adenine dinucleotide phosphate (NADP+; see picture) as well as occupying both the cofactor‐ and the substrate‐binding site in glucose‐6‐phosphate (G6P) dehydrogenase. This combination of two inhibition mechanisms makes the clip highly effective and selective for this enzyme over other dehydrogenases.