A gradient descent algorithm for minimizing amino acid coupling reactions when synthesizing cyclic-peptide libraries

Combinatorial chemistry has become an invaluable tool in medicinal chemistry for the identification of new drug leads. For example, libraries of predetermined sequences and head-to-tail cyclized peptides are routinely synthesized in our laboratory using the IRORI approach. Such libraries are used as molecular toolkits that enable the development of pharmacophores that define activity and specificity at receptor targets. These libraries can be quite large and difficult to handle, due to physical and chemical constraints imposed by their size. Therefore, smaller sub-libraries are often targeted for synthesis. The number of coupling reactions required can be greatly reduced if the peptides having common amino acids are grouped into the same sub-library (batching). This paper describes a schedule optimizer to minimize the number of coupling reactions by rotating and aligning sequences while simultaneously batching. The gradient descent method thereby reduces the number of coupling reactions required for synthesizing cyclic peptide libraries. We show that the algorithm results in a 75% reduction in the number of coupling reactions for a typical cyclic peptide library.     

Simulation of 200–400 Me V/u ~(12)C+~(12)C elastic scattering on SHARAQ spectrometer

In order to further obtain the information of three-body force(TBF) from 200–400 Me V/u12C+12C elastic scattering, we plan to perform this experiment on a SHARAQ spectrometer. Based on the experimental condition of the Radioactive Ion Beam Factory(RIBF)-SHARAQ facility, a simulation is given to find a compromise between the better energy and angular resolutions, and higher yield by optimizing the target thickness, beam transport mode, beam intensity and angular step. From the simulation, we found that the beam quality mainly limits the improvements of energy and angular resolutions. A beam tracking system as well as a lateral and angular dispersionmatching technique are adopted to reduce the influence of beam quality. According to the two angular settings of SHARAQ as well as the expected cross sections on the basis of the theoretical model, the energy and angular resolutions, and statistical accuracy are estimated.     

广义Lebesgue-Ramanujan-Nagell方程研究的新进展

广义Lebesgue-Ramanujan-Nagell方程是数论中一类重要的Diophantine方程.本文介绍了此类方程的近期结果和尚未解决的问题.     

HPLC-ELSD法测定绞股蓝中绞股蓝皂苷A的含量

采用HPLC-ELSD法测定绞股蓝中绞股蓝皂苷A的含量。色谱柱为HibarC18(250×4.6mm,5μm),流动相为乙腈-水梯度洗脱,流速0.5mL/min,柱温为20℃,绞股蓝皂苷A在0.0425—1.995mg/mL范围内线性关系良好(r2=0.9962),并通过正交法优化其提取工艺。该方法简便、有效,为绞股蓝的质量控制提供一种准确可行的检测方法。     

Schiff碱药物对产气杆菌代谢抑制的热力学研究

用微量热法测定产气杆菌在不同温度条件下受到Schiff碱药物抑制的热谱曲线, 根据其指数生长期的热谱信息, 确定它在不同温度条件下的生长速率常数和反应活化能, 找出了该细菌的最佳生长温度。同时借用化学反应中的过渡态理论, 得到一系列热力学参数, 对细菌在受到抑制时的生长代谢进行了热力学分析。     

三齿NS2型配体Cu(Ⅱ)配合物的合成、光谱性质及电化学性质

A variety of complexes Cu(NS₂)(Im)(NO₃)₂ and Cu(NS₂)(Py)(NO₃)₂ where NS₂=HN(CH₂CH₂SR)₂(R=CH₃CH₂CH₂, (CH₃)₂CH,CH₃CH₂CH₂CH₂ and (CH₃)₂CHCH₂), have been synthesized and characterized by elementary analyses, molar conductivity, IR, UV/Vis and ESR spectra as well as by electrochemical methods. The new complexes exhibit exceptionally high redox potentials(500～580 mV) and complexes for HN(CH₂CH₂SCH(CH₃)₂)₂ exihibit rather hyperfine splitting constants(a_‖<70G) in the powder ESR spectra, which are close to those for the blue copper proteins.     

An activated O --> N acyl transfer auxiliary: efficient amide-backbone substitution of hindered "difficult" peptides

Overcoming the phenomenon known as "difficult" synthetic sequences has been a major goal in solid-phase peptide synthesis for over 30 years. In this work the advantages of amide backbone-substitution in the solid-phase synthesis of "difficult" peptides are augmented by developing an activated N(alpha)()-acyl transfer auxiliary. Apart from disrupting troublesome intermolecular hydrogen-bonding networks, the primary function of the activated N(alpha)()-auxiliary was to facilitate clean and efficient acyl capture of large or beta-branched amino acids and improve acyl transfer yields to the secondary N(alpha)()-amine. We found o-hydroxyl-substituted nitrobenzyl (Hnb) groups were suitable N(alpha)()-auxiliaries for this purpose. The relative acyl transfer efficiency of the Hnb auxiliary was superior to the 2-hydroxy-4-methoxybenzyl (Hmb) auxiliary with protected amino acids of varying size. Significantly, this difference in efficiency was more pronounced between more sterically demanding amino acids. The Hnb auxiliary is readily incorporated at the N(alpha)()-amine during SPPS by reductive alkylation of its corresponding benzaldehyde derivative and conveniently removed by mild photolysis at 366 nm. The usefulness of the Hnb auxiliary for the improvement of coupling efficiencies in the chain-assembly of difficult peptides was demonstrated by the efficient Hnb-assisted Fmoc solid-phase synthesis of a known hindered difficult peptide sequence, STAT-91. This work suggests the Hnb auxiliary will significantly enhance our ability to synthesize difficult polypeptides and increases the applicability of amide-backbone substitution.     

Trace determination of platinum-II. Analysis in ores by pulse polarography after fire-assay collection

A pulse-polarography method is described for the determination of traces of platinum in ores after fire-assay separation and preconcentration. The silver bead from the fire assay is dissolved and treated with ammonia and ethylenediamine to produce a sensitive catalytic polarographic wave. Measurement of the wave by differential pulse polarography allows determination of Pt with a detection limit of 0.0025 ppm. Platinum in ore samples was determined in the range 0.1-0.9 ppm and a correlation coefficient of 0.98 was obtained on comparison with AAS results.     

A versatile synthetic approach to peptidyl privileged structures using a "safety-catch" linker

Peptidyl privileged structures have been widely used by many groups to discover biologically active molecules. In this context, privileged substructures are used as "hydrophobic anchors", to which peptide functionality is appended to gain specificity. Utilization of this concept has led to the discovery of many different active compounds at a wide range of biological receptors. A synthetic approach to these compounds has been developed on a "safety-catch" linker that allows rapid preparation of large libraries of these molecules. Importantly, amide bond formation/cleavage through treatment with amines is the final step; it is a linker strategy that allows significant diversification to be easily incorporated, and it only requires the inclusion of an amide bond. In addition, chemistry has been developed that permits the urea moiety to be inserted at the N-terminus of the peptide, allowing the same set of amines (either privileged substructures or amino acid analogues) to be used at both the N- and C-termini of the molecule. To show the robustness of this approach, a small library of peptidyl privileged structures were synthesized, illustrating that large combinatorial libraries can be synthesized using these technologies.     

Studies on NaXe Clusters

In this paper all NaCl crystal samples containing metallic sodium colloids used in experiments were cleaved to ~1mm thickness from a block of NaCl single crystal at room temperature1,2. Two parallel large surfaces of each crystal were polished. Then these NaCl crystal specimens were implanted at 10-6 Torr with xenon ions using an accelerating voltage of 36 keV. The xenon ion fluences were in the range from 1(1015/cm2 to 7(1017/cm2. The chemical shifts of 23Na in these NaCl crystal specime…