Selection of synthetic receptors capable of sensing the difference in binding of d-Ala-d-Ala or d-Ala-d-Lac ligands by screening of a combinatorial CTV-based library

Screening of a combinatorial CTV-based artificial, synthetic receptor library 1 {1-13, 1-13, 1-13} for binding of a variety d-Ala-d-Ala and d-Ala-d-Lac containing ligands (6-11) was carried out in phosphate buffer (0.1 N, pH=7.0). After screening and Edman sequencing, synthetic receptors were found containing amino acid sequences, which are either characteristic for binding dye labeled d-Ala-d-Ala or d-Ala-d-Lac containing ligands. For example, receptors capable of binding d-Ala-d-Ala containing ligands 6, 7, 9 and 11 contained—almost in all cases—at least one basic amino acid residue—predominantly Lys—in their arms. This was really a striking difference with the arms of the receptors capable of binding d-Ala-d-Lac containing ligands 8 and 10, which usually contained a significant number of polar amino acids (Gln and Ser), especially in ligand 8, but hardly any basic amino acids. Use of different (fluorescent) dye labels showed that the label has a profound, albeit not decisive, influence on the binding by the receptor. A hit from the screening of the CTV-library with FITC-peptidoglycan (6) was selected for resynthesis and validation.     

Isolation and characterization of an anti-recombinant erythropoietin single-chain antibody fragment using a phage display antibody library

The production of a large amount of specific antibodies against erythropoietin (EPO) is necessary for both clinical treatment and doping control. However, the weak immunogenicity of EPO and the side effects of excessive injection make the conventional immunological protocol rather inefficient and time-consuming. In this study, a single-chain antibody fragment of variable region (scFv) against recombinant human erythropoietin (rHuEPO) was produced after three rounds of panning a phage display antibody library. The selected scFv-B₂ was expressed in soluble form in Escherichia coli DH5α F′ and purified by His-bond nickel affinity chromatography with a yield of about 1–2 mg of antibody in 1 L of the culture supernatant. The molecular weight of the scFv was estimated to be 29 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis and the affinity constant was found to be 1.0×10⁸ L mol⁻¹ based on a competitive indirect enzyme-linked immunosorbent assay (CI-ELISA). The potential ability of the scFvs for immunopurification of rHuEPO from related sample was demonstrated by using a double-antibody sandwich ELISA. The reported method is a very powerful tool to produce specific antibodies for rHuEPO detection demands.     

基层图书馆工作与科技创新

基层图书馆应充分利用科技创新的有利时机,使用有限的图书资源和现有阅览条件,从提高馆员专业素质,科学管理,了解读者,增加藏书量等方面考虑,发挥图书服务读者、服务社区的作用。     

MALDI-TOF-MS用于组合化学肽库的鉴定

组合化学是一种快速制备大量相关化合物,并可快速对其进行生物活性筛选的革新性的技术和方法。组合化学法自问世以来在生命科学和医药科学技术等领域获得了飞速发展。组合化学肽库已成为同时制备大量不同序列多肽的方法,并已广泛用于抗原决定簇、生物分子相互作用、亲和抑制剂、新药筛选等研究。在亲和筛选研究中,合成组合肽库的评价以及结构鉴定是研究成败的关键步骤之一。     

Exploring privileged structures: the combinatorial synthesis of cyclic peptides

Head-to-tail cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. They may therefore be considered to be privileged structures. This review outlines the strategies by which both macrocyclic cyclic peptides and cyclic dipeptides or diketopiperazines have been synthesised in combinatorial libraries. It also briefly outlines some of the biological applications of these molecules, thereby justifying their inclusion as privileged structures.     

Synthesis of 7,8‐Dihydrothieno[3′,2′:4,5]pyrrolo[1,2‐a]pyrazin‐5(6H)‐ones Using a Modification of Four‐Component Ugi Reaction

We describe an efficient synthesis of novel 7,8‐dihydrothieno [3′,2′:4,5]pyrrolo[1,2‐a]pyrazin‐5(6H)‐one heterocyclic structures. The target compounds were prepared by a novel modification of four‐component Ugi reaction of heterocyclic bifunctional keto acids, isonitriles, and amines. We demonstrate the usefulness and versatility of the developed approach, which is amenable to production of combinatorial libraries.     

Negative asymptotic topological dimension, a new condensate, and their relation to the quantized Zipf law

We introduce the notion of weight for the asymptotic topological dimension. Planck’s formula for black-body radiation is refined. We introduce the notion of negative asymptotic topological dimension (of hole dimension). The condensate in the hole dimension is applied to the quantized Zipf law for frequency dictionaries (obtained earlier by the author).     

兆瓦级NBI加热系统弧流电源故障诊断方法探究

针对中国环流器2号A(HL-2A)装置弧流电源的特点，以及弧流电源故障诊断的条件与现状，提出了结合中性束注入(NBI)控制系统的相关功能模块与基于Matlab/Simulink仿真技术构建的故障字典，以实现弧流电源运行状态的在线监测及其故障模式的诊断。NBI控制系统在监测到弧流电源故障状态后，调用存储的弧流电源输出信号进行分析，提取信号的特征值，然后通过查找弧流电源故障字典以诊断出可能的故障模式。结合实验数据论证了该故障诊断法对弧流电源简单故障定位准确，对复杂故障能缩小定位范围，具有原理简单、可操作性强等优点。