Some novel approaches to the design and synthesis of peptide-catecholamine conjugates.
Some novel approaches to the design and synthesis of peptide-catecholamine conjugates.
复制标题
肽-儿茶酚胺缀合物的设计和合成的一些新方法。
DOI：
10.1002/bip.360220166
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发表时间：
1983
期刊：
影响因子：
2.9
通讯作者：
Goodman,M
中科院分区：
文献类型：
--
作者：
Verlander,MS;Jacobson,KA;Rosenkranz,RP;Melmon,KL;Goodman,M
已经合成了一系列新的官能化的儿茶酚胺（同类物），其中，从形式上讲，异丙肾上腺素的N-异丙基基团已经被不同长度的线性烷基链延长，并被羧基基团封端。还制备了模型酰胺衍生物，以优化这些衍生物的生物活性，并有助于设计用于合成缀合物的适当肽。作为这些研究的结果，制备了一系列氨基酸和单分散肽载体，含有对氨基苯丙氨酸作为药物的连接点，以及相应的缀合物。对同系物、模型酰胺和缀合物的体外和体内评价表明，这些衍生物的生物活性对远离药效团的结构修饰极其敏感，在同类物酰胺和共轭物系列中。许多模型酰胺和缀合物已被证明是高度活跃的，当在体外和体内测试系统测试。这些结果的影响方面的一种新的结构活性的药物设计方法进行了讨论。
A series of novel, functionalized catecholamines (congeners) has been synthesized in which, formalistically, theN‐isopropyl group of isoproterenol has been extended by a linear alkyl chain of varying length, terminated by a carboxyl group. Model amide derivatives have also been prepared in order to optimize the biological activity of these derivatives and also to aid in the design of appropriate peptides for the synthesis of conjugates. As a result of these studies, a series of amino acid and monodisperse peptide carriers, containingp‐aminophenylalanine as the point of attachment for the drug, was prepared, together with the corresponding conjugates.In vitroandin vivoevaluation of the congeners, model amides, and conjugates has demonstrated that the biological activity of these derivatives is extremely sensitive to structural modifications at a point far‐removed from the pharmacophore, in both the congener amide and conjugate series. A number of the model amides and conjugates have proven to be highly active when tested in bothin vitroandin vivotest systems. The implications of these results in terms of a novel structure–activity approach to drug design are discussed.