P6A及其类似物的构象研究  

Study on the Conformations of P6A and Derivatives

作　　者：赵明[1] 张亮仁[1] 于亭[1] 彭师奇[1] 周琴璐[1] 赵文忠[1] 李强[1] 

机构地区：[1]北京医科大学药学院生源药物化学研究室,北京市体育科学研究所

出　　处：《中国药物化学杂志》1996年第2期125-129,156,共6页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金

摘　　要：纤维蛋白β链的降解产物Ｐ６Ａ及相关的类似物，具有明确的血管效应。生物检测表明，当Ｐ６Ａ的Ｎ端用不同的氨基酸替代时，可以导致不同的结果。就舒血管作用而言，或增强Ｐ６Ａ的效应，或减弱Ｐ６Ａ的效应，或与Ｐ６Ａ相当，或无活性，因而是结构依赖的。本文采用Ｂｉｏｓｙ公司设计的Ｄｉｓｃｏｖｅｒ程序，计算了８种化合物可能的优势构象。结果表明，在α－右手螺旋、α－左手螺旋和β－伸展三种可能的构象状态中，８个化合物的β－伸展构象的总能量都比α－螺旋低，β－伸展可能就是它们在溶液中的构象。本文计算了分子中有重要影响的某些原子间距离以及二面角，发现舒血管活性最强的Ｇｌｎ－Ｐ６Ａ的有关二面角具有特殊性，这是一项有意义的发现。Degradation product of fibrinogen beta-chain, P6A and derivatives have vasoactive potency. The bioassay indicated that the modification of amino acid residue at the -terminal of P6A had important influence. In compound (1) and (2), the N-terminal residues are Lys1 and Arg1 respectively and the introduction with basic residue resulted in the abolition of relaxation action. In compound (3) and (5) the N-terminal residues are Asp1 and Glu1 respectively, the amino acids with acidic side were introduced and the related effect of P6A was converted into contraction. The N-terminal residues for compound (4) and (6) are Asn1 and Gln1 respectively, which have amide side chain, the relaxation effect of the former is approximately the same as that of P6A and the relaxation effect of the latter is approximately 6 times stronger as that of P6A. These results indicated the bioactivities of them were structure-dependent. In the present paper, the most stable comformations of P6A and (7) derivatives were calculated with discover program(Biosy Inc. ). It was shown that the total energy of β-strade is the lowest one in all three kinds of conformations of α-L-helix, α-R-helix and β-strade for these 8 compounds, suggesting β-strade may be their conformations in solution. Some important atomic distances and dihedral angles were also calculated here and Gln1-P6A had particular interesting values.

关 键 词：P6A 类似物 构效关系 构象 化学药理学 

分 类 号：R962[医药卫生—药理学]