Solution Structures and Spectra of VO(II)‐Serine‐Phenanthroline Ternary System

ESR spectra of VO(II)‐serine(Ser)‐phen system in binary solvent glycol/water (V/ V = 1:1) solution at various acidities (pH= 1‐14) have been observed at low temperature. It was found that in different pH ranges different structural complexes were formed. According to Johnson's rule and IR, their possible structures were suggested. The bonding parameters of complexes were calculated from ESR parameters. It can be seen that the or values of complexes decrease following the increasing of an N donor replacing the O donor of water on the equatorial plane in the complexes. This means that the covalent bonding between vanadium and ligands increases as amino and phen ligands replace water ligands. The crystal field parameters were calculated by using electronic spectral data. The coordination law was discussed. It was obtained that the coordination reactivity of phen is much stronger than that of Ser.     

One-pot synthesis of phenylphosphonic acid imprinted polymers for tyrosine phosphopeptides recognition in aqueous phase

The tyrosine phosphorylation of proteins plays a vital role in signal transduction pathways. The highly selective enrichment of tyrosine phosphopeptides remains a significant challenge in this area of research because of the low levels of tyrosine phosphorylation in cells. Herein, we report the development of a novel molecularly imprinted polymer (MIP)-based method for the recognition of tyrosine phosphopeptides in aqueous media using an epitope approach. Phenylphosphonic acid, which has been regarded the “epitope” of phosphotyrosine, was used as a template, and commercially available zinc acrylate was used as a functional monomer to prepare the MIP. The one-pot synthetic process was simple, efficient, and the resulting MIPs were low-cost, robust, and recyclable. The MIP demonstrated significant higher levels of adsorption capacity and selectivity for phenylphosphonic acid than the non-imprinting polymer (NIP) over its structural analog benzoic acid. The MIP was also used as a molecular receptor to recognize tyrosine phosphopeptides in aqueous media, and showed a clear preference for tyrosine phosphopeptides over interfering serine peptides compared to TiO₂. These results revealed the feasibility of the use of MIPs to effectively mimic the epitope approach, and provided a promising alternative to the immunoaffinity techniques commonly used for capturing tyrosine phosphopeptides.     

Efficient synthesis of α-aryl serine derivatives via three-component reactions of aryldiazoacetates,anilines and formaldehyde

A three-component reaction based on trapping of ammonium ylides with formaldehyde was first reported. This reaction offers a new strategy for the synthesis of α-aryl serine derivatives and can be extended to the preparation of α-aryl threonine derivatives. Synthetic application of the three component reaction for the preparation of hydroquinoxaline derivative was also demonstrated.     

Immobilized enzymes and cells in poly(N-vinyl caprolactam)-based hydrogels

A one-step mild method for entrapping animal cells and enzymes in macroporous composite poly (N-vinyl caprolactam)-calcium alginate (PVCL-CaAlg) hydrogels is described. Some properties of immobilized enzymes, such as thermal and storage stabilities and stability in water/organic media were investigated. Composite PVCL-CaAlg gels were successfully applied to immobilize a number of proteases, namely, trypsin, α-chymotrypsin, carboxypeptidase B, and thrombin. Thermal stability of the immobilized preparations obtained by entrapment in hydrogel beads allowed us to use them at 65–80†C, while the native enzymes were completely inactivated at 50–55°C. Various applications of enzymes and cells immobilized in beads weredemonstrated. Immobilized trypsin and carboxypeptidase B were applied to prepare human insulin from recombinant proinsulin. The hydrogel beads with entrapped α-chymotrypsin were used in enantioselective hydrolysis of Shiff's base of D,L-phenylalanine ethyl ester (SBPH) in acetonitrile/water medium. Thrombin immobilized in PVCL-based hydrogel films was shown to be a promising compound for wound treatment. To prepare pure preparations of monoclonal antibodies (MAb) several hybridoma cell lines, including hybridoma cell lines producing MAb to interleukin-2, were successfully cultivated in the hydrogel beads.     

Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment‐Based Drug Design Facilitated by Dynamic Combinatorial Chemistry

Fragment‐based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit‐identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X‐ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis‐acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC₅₀ value of 54 nm , which represents a 240‐fold improvement in potency compared to the parent hits. Subsequent X‐ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit‐identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit‐to‐lead optimization.     

Heat capacity of <Emphasis Type="Italic">D</Emphasis>- and <Emphasis Type="Italic">DL</Emphasis>-serine in a temperature range of 5.5 to 300 K

Heat capacity of D- and DL-serine was measured using adiabatic calorimetry in a temperature range of 5.5 to 300 K, and then thermodynamic functions were calculated. The difference in heat capacity (C _PD-C _PDL) between two species indicates a small anomaly in D-serine near 15 K and a systematic excess over DL for temperatures > 30 K. This is much larger, than a difference in thermodynamic functions measured so far for the polymorphs of organic molecular crystals. The excess is fitted well to Einstein contribution with characteristic temperature of 185 K which is equivalent to vibrational mode at 129 cm⁻¹.     

丙型肝炎病毒抑制剂的三维药效团和构效关系

通过ＣＡＴＡＬＹＳＴ软件包得到了两类ＨＣＶ ＮＳ３丝氨酸蛋白酶抑制剂的三维药效团模型。尽管这两类抑制剂具有完全不同的骨架结构,但得到的药效团却具有共同的特性。这当这两类抑制剂和受体发生相互作用时,可能采用了相似的结合模式。根据药效团模型,进行了三维构效关系的研究。结果表明,得到的药效团模型具有良好的预测能力（线性回归系数Ｒ＝０．８９）。