特殊氢原子与丙氨酸二肽构象稳定性的理论研究

使用B3LYP／6-31G^*方法，优化得到了丙氨酸二肽分子的6个稳定构象，从特殊氢原子之间的相互作用及其所形成氢键环和五元环的结构特点，探讨了影响二肽构象稳定性的因素，并估算了相关弱相互作用的能量。     

环苯丙—精二肽盐酸盐水合物的合成及生理活性研究

本文报道了环苯丙-精二肽盐酸盐水合物1的合成及其生理活性研究。作者首次使用DCC/Na_2CO_3合成肽键,无需复杂的纯化,产品纯度较高,产率达83％。本文用此法合成了另外6种二肽。药理试验显示,1对免疫系统有广泛的增强作用并显示出较强的抗肿瘤活性,其机制可能与其免疫促进作用有关。     

Synthesis of N-(2-hydroxy-1-phenoxyacetyl) prolyproline

Ionophores consist of molecules which surround and carry positive metal ions and other ions through biological membranes. One classe of ionophores which we have been developing contains dipeptides which are encouraged to become part of a ring because of possible hydrogen bond formation between the 2-hydroxy on the phenyl group and carboxyl group (COOH) of the final amide proline. Formation of a ring should increase the complexation ability of the ionophore. We report that the synthesis of N-(2-hydroxyl-1-phenoxyacetyl) prolyproline(1), a novel ionophore is prepared from activated 2-acetoxy phenoxyacetic acid (3a) and the appropriate dipeptide ester using coupling methods such as dicyclohexyl carbodiimide with hydroxyben-ztriazole or carbonyl diimidazole. Yang Dingqiao: born in 1958, Associate professor     

基于3种建模法的食源性 ACE抑制二肽 QSAR 研究

以自组建的食源性血管紧张素转化酶（angiotensin I‐converting enzyme ,ACE）抑制二肽为研究样本,采用氨基酸描述子VHSE（principal component score vector of hydrophilicity ,steric ,and electronic properties）对ACE抑制二肽进行表征后,比较偏最小二乘（partial least square regression ,PLS）、支持向量机（support vector machine ,SVM）及主成分分析（principal component analysis ,PCA）‐SVM相结合的3种建模方法对ACE抑制二肽的QSAR（quantitative structure‐activity relationship）建模。结果显示,对于食源性ACE抑制二肽,3个模型的拟合能力无明显差异,SVM模型的预测能力略强;对其进行权重投影分析发现,C末端氨基酸较N末端氨基酸对其活性的影响更为明显。     

环（L-丙-L-脯）二肽的合成

以L-(+)-丙氨酸和N-叔丁氧羰基-L-(+)-脯氨酸为原料,分别经中和、缩合、脱保护、环化反应后,以65.3%的总产率合成得到了新型催化剂环(L-丙-L-脯)二肽,结构经IR、1HNMR、13CNMR、元素分析等表征.     

碱基与氨基酸二肽间的氢键相互作用

对于碱基-蛋白质之间的相互作用,氢键的形成及断裂起着重要的作用.选取7种氨基酸二肽和3种碱基,以它们之间形成单根氢键的体系为研究对象,在ab initioB3LYP/6-311++G(d,p)水平下进行结构优化,MP2/6-311++G(d,p)水平下进行能量的计算.同时应用ABEEMσπ/MM方法优化结构和计算能量.通过改变氢键相互作用区域的静电相互作用参数kH-bond和形成氢键的氢原子与其受体原子的孤对电子之间距离Rlp,H来拟合函数kH-bond(Rlp,H).用所得函数对选取的复合物进行结合能计算,其结果与ab initio方法所得的结果符合的很好.     

利用ABEEM/MM模型对气态丝氨酸和苏氨酸残基二肽分子构象的研究

应用ABEEM／MM浮动电荷模型（原子一键电负性均衡方法融合进分子力场）对气态丝氨酸和苏氨酸残基二肽分子构象进行了初步的研究，与经典的力场模型相比，该方法中的静电势包含了分子内和分子间的静电极化作用，以及分子内电荷转移影响，同时加入了化学键等非原子中心电荷位点，合理的体现了分子中的电荷分布。相对其他极化力场模型，该模型具有计算量较小的特点。结果表明：我们模型计算的两种二肽分子的构象能和关键二面角结构与从头计算结果符合得很好，优于其他力场模型。     

Leishmania donovani in hamsters: Stimulation of non-specific resistance by novel lipopeptides and their effect in antileishmanial therapy

Several novel type of lipopeptides were synthesized and evaluated for their ability to stimulate non-specific resistance againstLeishmania donovani infection. Peritoneal macrophages isolated from young male hamsters treated with muramyl dipeptide (MDP) and various synthetic lipopeptides (6 mg/kg i.p.) 7 days earlier, were cultured in vitro and challenged 24 h later withL. donovani promastigotes. One lipopeptide, Central Drug Research Institute (CDRI) compound 86/450, exhibited significantly higher immunostimulatory activity than MDP. Its prophylactic activity was further confirmed in hamsters by giving 2 split doses of 3 mg/kg of the compound spaced at 2 weeks, i.e. on day –7 and +7 of challenge withL. donovani amastigotes. The prophylactic effect lasted for 7 days following the last treatment with compound 86/450. The antileishmanial action of sodium stibogluconate (SAG) was also found to be enhanced by 16% in hamsters primed with compound 86/450.CDRI Communication No. 5034.     

组氨酸二肽-水团簇的Ab Initio和ABEEMσπ力场的研究

使用密度泛函B3LYP/6-311++G(d,p)方法对组氨酸二肽与水团簇的结构进行优化,在MP2/aug-cc-pVDZ水平下计算了这些体系的结合能,同时考虑了基组重叠误差(BSSE)和零点能(ZPE)校正.应用ABEEMσπ浮动电荷分子力场优化了组氨酸二肽与水分子所形成的团簇结构,计算了氢键键长和氢键键角,同时计算了组氨酸二肽与1~6个水分子所形成的团簇His(H2O)n(n=1~6)的结合能,探讨了氢键的协同效应.将ABEEMσπ浮动电荷分子力场、OPLSAA和AMBER力场所得的结果与从头算方法的结果进行了比较,ABEEMσπ的结果好于OPLS-AA和AMBER力场的,可与从头算方法所得到的结果相媲美.