生长激素释放肽促生长的免疫调节

采用固相法合成了生长激素释放肽（ＧＨＲＰ）,研究了其促生长及免疫调节活性,腹腔连续注射（ｉｐ）１００,３００,１０００,５０００μｇ／ｋｇ ＧＨＲＰ１０ｄ后,发现小鼠体重对照组显明增加;复腔连续细胞（ＰＭΦ）精氨酸酶（Ａｒｇｉａｓｅ）,酸性磷酸酶（ＡＣＰ）活性提高约５０％;红细胞Ｃ３ｂＲ及ＩＣ花环率、血清溶血素含量增加８０％左右,提示ＧＨＲＰ具有免疫调节活性。     

高效液相色谱法测定鲑鱼降钙素及其注射液中含量

选择优化的HPLC色谱条件 ,用梯度洗脱法分离测定原药及注射液中鲑鱼降钙素的含量。以Vydac 2 1 8TP54C1 8柱 (4.6× 2 50mm ,30 0 0A ,5μm )作分析柱 ,流动相∶A液为 0 .0 5mol L磷酸二氢钠缓冲液 (pH =3.0 ) ,B液为A液 +乙腈 (2∶3)。梯度洗脱∶B液在 2 0min内从 45%增加至 70 %。检测波长为 2 1 5nm。方法的精密度、线性关系、回收率均良好 ,和生物测定法相比较 ,本法简便、快速、经济 ,测定结果较为满意。并用建立的方法考察原药及其注射液的稳定性。     

组合化学在新药研究中的应用

综述了组合化学在新药研究中的应用,着重介绍了小分子库、肽化学库和药物筛选．     

鳙鱼肽的抗衰老和免疫调节作用

利用D-半乳糖致衰小鼠模型,观察了鳙鱼肽对衰老模型小鼠免疫器官指数及吞噬能力的影响,以及对小鼠血清、肝脑组织中丙二醛（MDA）、超氧化物岐化酶（SOD）、谷胱甘肽过氧化物酶（GSH—Px）及单胺氧化酶（MAO—B）等的影响,并从细胞器——线粒体角度探讨了鳙鱼肽对Ca^2＋泵和Na^＋泵的作用．结果表明：鳙鱼肽可明显降低致衰小鼠肝脑组织中MDA的含量;降低脑组织中MAO—B的活性（P〈0．01）;提高抗氧化酶SOD和GSH-Px的活性;同时对线粒体中Na^＋泵和Ca^2＋泵的活力也有显著影响,能显著提高致衰小鼠吞噬细胞的吞噬能力（P〈0．01）．说明鳙鱼肽对D-半乳糖致衰小鼠有明显的抗衰老和免疫调节作用．     

酶解法制备乌鸡蛋白肽的动力学研究

以乌鸡蛋白为底物,研究了木瓜蛋白酶在酶解乌鸡蛋白制备乌鸡蛋白肽时的一级热失活、拟态条件下的米氏常数,建立了考虑底物反竞争性抑制和产物竞争性抑制等影响因素下的反应动力学模型,并根据实验结果求得在70℃下的酶催化水解反应动力学常数Kd为0.011 3min-1,Km为5.70×10-3mol/L,Kcat为1.589 8min-1,并得到了相应的水解度动力学模型和反应速度动力学模型.     

氧化酪蛋白对小鼠组织抗氧化能力及血液肽组成的影响

目的研究酪蛋白经过加热氧化和脂质过氧化物MDA氧化后,对小鼠体内氧化还原状态及小鼠血液中肽组成的影响。方法酪蛋白经100℃加热（0、30、60、90min）和丙二醛（MDA）氧化（MDA终浓度0、0．2、20、200mmol／L）处理,测定其羰基、巯基含量及表面疏水性的变化。小鼠分为四组,分别灌胃生理盐水、正常酪蛋白、加热90rain、MDA氧化酪蛋白,测定0、30、60、90、120、160min血液中自由基水平,并采用HPLC-MS分析灌胃后120min小鼠血浆肽组分的变化,测定小鼠的肝脏、空肠、十二指肠组织抗氧化能力指标（总抗氧化能力T—AOC、丙二醛MDA、还原型谷胱甘肽GSH）。结果酪蛋白经过两种氧化处理,羰基含量均随氧化程度呈显著上升,巯基含量呈下降趋势。加热氧化后酪蛋白表面疏水性比正常酪蛋白低,而MDA氧化导致疏水性上升。小鼠血液中自由基最高峰出现在灌胃后160min。灌胃两种方式处理的酪蛋白,血液中自由基的含量均显著高于灌胃正常酪蛋白组（P〈0．05）,肝脏、空肠、十二指肠还原型谷胱甘肽（GSH）含量和总抗氧化能力（T-AOC）均低于正常酪蛋白组,丙二醛（MDA）含量显著提高（P〈0．05）。HPLC—MS分析显示,灌胃MDA氧化酪蛋白组血液中肽组成与对照组不同,出现c7H15N4O含羰基类的物质：结论氧化会导致酪蛋白理化性质的改变,摄入氧化酪蛋白引起机体的氧化应激,降低组织抗氧化能力。     

Molecular characterization and expression of the antimicrobial peptide defensin from the housefly (Musca domestica)

A 430-bp cDNA encoding the insect antimicrobial peptide defensin was cloned from the housefly, and designated Musca domestica defensin (Mdde). The open reading frame of the cDNA encoded a 92-amino acid peptide with an N-terminal signal sequence followed by a propeptide that is processed by cleavage to a 40-amino acid mature peptide. Northern analysis and in situ hybridization identified the corresponding mRNA in the fat body of bacterially challenged houseflies and in the epidermis of the body wall of naive and challenged houseflies. The Gram-negative bacterium (Escherichia coli) is a strong inducer of the gene. By RT-PCR, Mdde mRNA was also detected in naive and challenged insects. These findings suggest that the defensin gene is constitutively expressed in the epidermis of the housefly body wall. The predicted mature form of Mdde was expressed as a recombinant peptide in E. coli and Pichia pastoris. The recombinant Mdde expressed in Pichia was active against Gram-positive and some Gram-negative bacteria. Received 20 June 2006; received after revision 3 October 2006; accepted 30 October 2006     

The translocation motif of hepatitis B virus improves protein vaccination

Cell-penetrating peptides (CPPs) have been shown to improve antigen loading of dendritic cell vaccines. Here we asked whether fusion of a CPP to a protein improves its immunogenicity when this fusion protein is directly applied as vaccine. We used the cell-penetrating translocation motif (TLM) derived from the hepatitis B virus, because no size limitation of cargos has been observed. Increased immunogenicity was observed when TLM was fused to ovalbumin (TLM-ova). TLM-ova was found to be superior to ova in inducing proliferation and cytotoxicity of ova-specific CD8+ T cells in vitro and in vivo. Using ovalbumin-expressing thymoma cells (EG7-ova), an improved anti-tumor immune response was observed for TLM-ova vaccination versus vaccination with ova. Moreover, TLM-ova vaccination induced a higher titer of anti-ovalbumin IgG2a antibodies compared to ova. These data demonstrate that CPP-protein vaccines can improve cellular as well as humoral immune responses. Received 16 November 2005; received after revision 12 December 2005; accepted 10 January 2006 †These authors contributed equally to this work     

Hydra – ancient model with modern outfit

The control of growth and differentiation is a central question not only for developmental biologists but increasingly for medical research as well. The freshwater polyp hydra was one of the first organisms to be used as a model system for the study of this question. It was chosen because of its simple body plan and because it is made up of only seven to eight different cell types. Recent research has shown that despite their simple body plan, cnidarians already exhibit an impressive repertoire of molecular tools which are responsible for the control of growth and differentiation and amongst which peptides appear to play an important role. Received 25 April 2007; received after revision 31 July 2007; accepted 28 August 2007     

迷向周期和方法在β-簮结构折褶模拟中的应用

采用新近提出的迷向周期和方法(IPS),结合自导Lang evin动态模拟,模拟研究9余肽折褶成β簮结构的情况,表明了该结构与NMR观察到的基本一致,而Ewald模拟由于是强烈的镜像相互作用会产生构型偏差,获得致密构型的几率增大,表明IPS方法更适合于周期边界条件的模拟.