曼氏血吸虫谷胱甘肽S—转移酶Sm26／2抗原肽研究

在计算机辅助下，应用Ｇｏｌｄｋｅｙ和ＰＣ－Ｇｅｎｅ程序，根据新报道的曼氏血吸虫谷胱甘肽Ｓ－转移酶Ｓｍ２６／２的氨基酸序列，进行亲水性、柔韧性、可接近性、电荷分布和二级结构分析，预测出６个抗原肽，并用固相法进行了合成。经Ｄｏｔ－ＥＬＩＳＡ法测定，其中的２个对抗日本血吸虫免疫球蛋白多克隆抗体（抗－Ｓｉ－ＩｇＧ－ＰｃＡｂ）显示出较好的抗原性，１个对抗血吸虫表膜单克隆抗体（Ａ６ＭｃＡｂ）显示出较好的抗原性     

曼氏和日本血吸虫副肌球蛋白的抗原肽研究

副肌球蛋白是世界卫生组织选取的用来发展血吸虫疫苗的重要侯选蛋白之一。 在计算机辅助下，应用PC－Gene程序，根据曼氏和日本血吸虫副肌球蛋白的氨基酸 序列，通过对其亲水性、柔韧性、可接近性和二级结构分析预测出8个抗原肽，并 用固相法进行了合成。经Dot-ELISA法测定，其中的2个对抗日本血吸虫免疫球蛋白 多克隆抗体（抗－Sj-IgG-PcAb)显示出抗原性，可作为抗血吸虫病合成多肽疫苗的 候选肽段。     

曼氏血吸虫合成多肽抗原研究

在计算机的辅助下，根据曼氏血吸虫２６ＫＤａ谷胱甘肽Ｓ－转移酶的氨基酸序列，通过对其亲水、柔韧性、可接近性、电荷分布和二级结构的分析来预测出６个抗原肽，并用固相法进行了合成。经Ｄｏｔ－ＥＬＩＳＡ法测定，其中的２个对抗日本血吸虫免疫球蛋白多克隆抗体（抗－ＳＪ－ＩｇＣＰｃＡｂ），１个对抗血吸虫表膜单克隆抗体（Ａ６ＭｃＡｂ）均显示良好的抗原性。     

苯二氮杂卓类化合物的合成及抗血吸虫活性研究

化合物B30属于苯二氮杂卓类化合物.体外实验表明,在50μM具有100％的杀灭血吸虫效果.本文利用药物化学生物电子等排等原理,设计、合成了4个B30衍生物6、10、13、16,并对其抗血吸虫活性进行初步体外评价.结果显示4个化合物均具有一定的杀虫能力.尤其化合物16有较好的抗血吸虫活性,在50μM浓度下血吸虫的存活率降...     

2-氯喹啉-3-甲醛缩氨基胍衍生物的合成及其抗菌活性评价

为寻找新的高活性的广谱抗菌剂,通过活性拼接原理,设计合成了8个未见文献报道的2-氯喹啉-3-甲醛缩氨基胍衍生物,并通过光谱方法确证结构.所合成化合物对所选的菌种(除了Salmonella typhimurium 2421和Pseudomonas aeruginosa 2742)均显示出了较好的抑制活性,最低抑菌浓度值(MIC)范围大都为2.0~16μg/m L.化合物4h显示出最好的广谱抗菌活性,其对抗所选的6种菌株的最低抑菌浓度值均为2.0μg/m L.其对抗Staphylococcus aureus KCTC 503和两种耐药菌(Methicillin-resistant Staphylococcus aureus CCARM 3167和Quinolone-resistant Staphylococcus aureus CCARM 3505)的活性要优于或相当于阳性对照药加替沙星、莫西沙星、诺氟沙星和苯唑西林.     

苯并硫氮杂卓类化合物作为抗血吸虫药物的研究

体外筛选实验发现:苯并硫氮杂卓类化合物B_(30),在50μM浓度时,可以完全杀灭日本血吸虫。本文以B_(30)为先导化合物,通过药物化学中的生物电子等排原理对其进行结构改造,设计并合成了11个B_(30)的类似物。对这些化合物进行体外抗血吸虫效果的评价,发现其中一个化合物A9的活性较好:其对血吸虫童虫和成虫的IC50分别为7.30μM和12.0μM,较先导化合物B_(30)IC50值降低了一倍。     

反相高效液相色谱/电喷雾质谱法分析化学合成七肽粗产物

利用RP—HPLC／ESI—MS直接分析用芴甲氧羰基(Fmoc)固相多肽合成方法在PHB树脂上偶联合成的一个七肽(H2N—Tyr—Val—Asn-Thr-Asn—Met—Gly—COOH,Mr797．3)粗产物。RP—HPLC显示合成粗产物含有1个主成分,4个次要成分和多个微量成分;与之联用的电喷雾质谱则同步准确地测定出各成分的分子量(m／z)并自动对各主要成分的化学结构进行了串联质谱分析。结果证明,粗产物中的主成分即为目标七肽,另外几个主要副产物为七肽的氧化产物或残缺肽。     

苯并噻嗪酮类化合物抗血吸虫活性的研究

本文以苯并噻嗪酮为母核,设计合成了12个新化合物,对其进行体外抗日本血吸虫活性研究,发现化合物A5的活性较好,对日本血吸虫童虫和成虫的IC50分别为12.2μM和6.8μM。     

构象锁定HIV-1融合抑制剂的合成及抗HIV-1活性研究

西夫韦肽(SFT)是一种有效抗HIV-1(Human Immunodeficiency Virus-1)融合抑制剂,它比已上市融合抑制药物T20拥有更高的药效及药代稳定性,目前已完成了IIb临床实验.以西夫韦肽为模板,通过构象锁定策略将多肽中原有的盐桥替换为共价键合成了SFT订书肽SFT-1和SFT-2.产物结构经圆二光谱确认形成了α-螺旋.对所有合成多肽进行了抗HIV-1活性检测,结果表明SFT订书肽对7个HIV-1假病毒株抑制活性均高于SFT,其中SFT-1对B'亚型和B'C重组亚型病毒株抑制活性最高,SFT-2对B、CRF01_AE和CRF08_BC亚型病毒株抑制活性最高.     

O-(硫杂蒽酮-[2]-基)-氧乙酸的合成研究

硫杂蒽酮化合物是合成许多有机化合物的重要中间体,在370~385 nm有很强的吸收能力[1-2],它避免了稀释单体对皮肤和眼睛的刺激以及挥发性有机化合物对人体的损害和对环境的污染,可作为印刷制版材料、印刷线路板的光致抗蚀剂、光固化油墨、光固化表面涂层材料等,在医药、染料、印刷等行业中有非常广泛的应用.同时,硫杂蒽酮化合物也是一种非常重要的医药合成中间体.2-氯-N,N′-二甲基硫杂蒽酮(泰尔登)是较好的抗抑郁症安定类药物[3-4].1-[2-(二乙胺)乙基]-4-羟甲基硫杂蒽酮(海蒽酮,Hycanthone)有较强的抗曼氏血吸虫作用,结构与放线霉素D和柔红霉素相似,其抗肿瘤试验显示:以嵌入方式与DNA结合,对组织培养的肿瘤细胞有作用,并对W-256、L1210、P815肥大细胞瘤有明显的抑制作用,但是无骨髓抑制作用[5].Sydney Archer等人[6-7]合成了一系列甲硫蒽酮类羟基衍生物,均有很好的抗肿瘤活性.     

日本血吸虫26ku谷胱甘肽S－转移酶Sj26抗原肽研究

多肽疫苗;日本血吸虫26ku谷胱甘肽S－转移酶Sj26抗原肽研究     

Prediction, Synthesis and Antigenicity of the Antigenic Peptides of 26kDa Glutathione S-Transferasc of Schistosoma Japonicum (Sj26)

Schistosomiasisisaworldwideparasiticdiseasethataffectsmorethan200millionpersonsin70countriesallovertheworld.Itisveryimportanttodevelopaneffectivevaccineincludingsignificantlevelsofprotectionagainsttheinvasivestageoftheparasiteforthepreventionofrapidr...     

Peptide Nanofibers Modified with a Protein by Using Designed Anchor Molecules Bearing Hydrophobic and Functional Moieties

Self‐assembly of peptides and proteins is a key feature of biological functions. Short amphiphilic peptides designed with a β‐sheet structure can form sophisticated nanofiber structures, and the fibers are available as nanomaterials for arranging biomolecules. Peptide FI (H‐PKFKIIEFEP‐OH) self‐assembles into nanofibers with a coiled fine structure, as reported in our previous work. We have constructed anchor molecules that have both a binding moiety for the fiber structure and a functional unit capable of capturing target molecules, with the purpose of arranging proteins on the designed peptide nanofibers. Designed anchors containing an alkyl chain as a binding unit and biotin as a functional moiety were found to bind to peptide fibers FI and F2i (H‐ALEAKFAAFEAKLA‐NH₂). The surface‐exposed biotin moiety on the fibers could capture an anti‐biotin antibody. Moreover, hydrophobic dipeptide anchor units composed of iminodiacetate connected to Phe–Phe or Ile–Ile and a peptide composed of six histidine residues connected to biotin could also connect FI peptide fibers to the anti‐biotin antibody through the chelation of Ni²⁺ ions. This strategy of using designed anchors opens a novel approach to constructing nanoscale protein arrays on peptide nanomaterials.     

Epitopic Peptides Identified by LC?CELISA and LC?CMS

A new strategy of a liquid chromatography (LC)-enzyme linked immunosorbent assay (ELISA) combined with liquid chromatography-mass spectrometry (LC?CMS) was developed to identify the epitopic peptides for the antigen in Streptococcus suis. Metallendopeptidase, a potential antigen for S. suis, was digested by trypsin. The tryptic solution was separated by LC under optimal condition and collected into tubes. After it was dried using a cooling vacuum, the immunogenecity of peptides in each tube was investigated by ELISA against its corresponding antibody. All peptides in each tube with positive signals based on ELISA results were identified by LC?CMS. Accordingly, six putative peptides of metallendopeptidase were found and synthesized, all of which possessed high antigenicity recognized by the antibody.     

Filaggrin Peptides with β‐Hairpin Structure Bind Rheumatoid Arthritis Antibodies

In the early detection of rheumatoid arthritis (RA) synthetic filaggrin peptides serve as antigens for rheumatoid‐specific autoantibodies (anti‐citrullinated peptide antibody, ACPA) in ELISA tests. In this work we present a peptide that exhibits the binding epitope of ACPA in the form of a stable folding β‐hairpin. The homogeneity of the peptide folding was confirmed by NMR spectroscopy and might lead to the first proposed structure of the antibody‐bound conformation of the epitope.     

STUDY ON PREPARATION AND APPLICATION OF MONOCLONAL ANTIBODIES TO Anabaena azollae

Forty hybridoma cell lines secreting monoclonal antibodies against Anabaena azollae have been established by fusing SP_2/O myeloma cells with spleen cells from BALB/c mice immunized with purified antigen Anabaena azollae from different strains of azolla.According to the fluorescent antibody test, 40 McAbs were divided into 8 types. They may differentiate the Anabaena azollae in 195 azolla strains which are collected from different places in the world, into 8 antigenic groups.The identifying result of Anabaena azollae isolated from reconstituted azolla and sexual hybrid azolla showed that the Anabaena azollae in the reconstituted azolla retains its antigenicity from the donor azolla, and Anabacna azollae in hybrid azolla maintains its antigenicity from the female parent plant.     

Novel and Convenient Method for the Preparation of Phosphonate Peptides and Phosphonamidate Peptides

Phosphonate and phosphonamidate peptides are phosphorus analogues of natural peptides. They have been great used as stable mimetics of tetrahedral transition states as enzyme inhibitors and as haptens for catalytic antibody research in recent years. Although several methods are available for the preparation of phosphonate peptides and phosphonamidate peptides, all of them use phosphonic acid derivatives as starting materials. The overall yields from the synthesis of phosphonic acid derivatives to desired peptides are not satisfactory in most cases.     

Performance and selectivity of polymeric pseudostationary phases for the electrokinetic separation of amino acid derivatives and peptides

Two polymeric pseudostationary phases, one an acrylamide polymer and the second a siloxane polymer, have been investigated for the separation of naphthalene-2,3-dicarboxaldehyde (NDA)-derivatized amino acids and small peptides. The dervatized amino acids were detected by UV absorbance and laser-induced fluorescence (LIF) detection. The polymers provided very high efficiency and good selectivity for the separation of the amino acids. The separation selectivity using the polymers was significantly different from that of SDS micelles, and there were subtle differences in selectivities between the polymers. Although very good detection limits were obtained with LIF detection, a significant background signal was observed when the polymers were not washed to remove fluorescent impurities. The polymers did not separate the peptides very well. It is postulated that the fixed covalent structure of the polymers prevents them from interacting strongly or efficiently with the peptides, which are large in relation to the analytes typically separated by electrokinetic chromatography using polymers.     

Natural Compounds against Alzheimer’s Disease: Molecular Recognition of Aβ1–42 Peptide by Salvia sclareoides Extract and its Major Component,Rosmarinic Acid,as Investigated by NMR

Amyloid peptides, Aβ1–40 and Aβ1–42, represent major molecular targets to develop potential drugs and diagnostic tools for Alzheimer’s Disease (AD). In fact, oligomeric and fibrillar aggregates generated by these peptides are amongst the principal components of amyloid plaques found post mortem in patients suffering from AD. Rosmarinic acid has been demonstrated to be effective in preventing the aggregation of amyloid peptides in vitro and to delay the progression of the disease in animal models. Nevertheless, no information is available about its molecular mechanism of action. Herein, we report the NMR characterization of the interaction of Salvia sclareoides extract and that of its major component, rosmarinic acid, with Aβ1–42 peptide, whose oligomers have been described as the most toxic Aβ species in vivo. Our data shed light on the structural determinants of rosmarinic acid–Aβ1–42 oligomers interaction, thus allowing the elucidation of its mechanism of action. They also provide important information for the rational design of new compounds with higher affinity for Aβ peptides to generate new anti‐amyloidogenic molecules and/or molecular tools for the specific targeting of amyloid aggregates in vivo. In addition, we identified methyl caffeate, another natural compound present in different plants and human diet, as a good ligand of Aβ1–42 oligomers, which also shows anti‐amyloidogenic activity. Finally, we demonstrated the possibility to exploit STD‐NMR and trNOESY experiments to screen extracts from natural sources for the presence of Aβ peptide ligands.     

含有甘氨酸的Keggin型杂多蓝的合成和抗艾滋病毒(HIV-1)活性研究

采用控制电位电解方法,制得8种含有甘氨酸的Keggin型钨系杂多蓝配合物．通过IR,UV-vis,^H NMR,^183W NMR,XPS等方法对其结构进行了表征．这类化合物具有较强的抗碱解能力．在MT4细胞内,对合成化合物进行了抗艾滋病毒(HIV-1)活性及毒性测定,发现该类化合物的抗艾滋病毒(HIV-1)活性随着还原电子数增多有增强的趋势,其中含有甘氨酸的十二钨锗酸4电子杂多蓝(代号HPBG-110)有较高的治疗指数(TI)．初步的试验结果表明：该类化合物的抗HIV-1活性作用是在病毒感染早期,通过抑制艾滋病毒(HIV-1)在靶细胞表面吸附而发挥作用的．