Stereoselective synthesis and structure determination of a bicyclo[3.3.2]decapeptide
Stereoselective synthesis and structure determination of a bicyclo[3.3.2]decapeptide
复制标题
DOI：
10.3998/ark.5550190.p008.500
复制
发表时间：
2014-01-01
期刊：
影响因子：
0.9
通讯作者：
Reymond, Jean-Louis
中科院分区：
文献类型：
--
作者：
Bartoloni, Marco;Waltersperger, Sandro;Reymond, Jean-Louis
通过类比有机分子内原子之间的共价键网络的结构多样性，我们可以通过将氨基酸分配给图节点并将肽键分配给图边来从数学图设计拓扑多样化的肽。关键是使用二氨基酸或氨基酸二酸作为三价图节点的等价物，这使得能够实现天然肽中标准线性和单环图之外的各种图拓扑。这里制备了双环十肽 A(1)FGk(2)VFPE(1)AG(2) (1b) 并结晶以指定其桥立体化学。桥构型按照分支氨基酸的手性所计划的那样出现。此外，双环化还取决于分支氨基酸中是否存在匹配的手性。第二个桥的立体选择性形成为合成一大类双环肽作为有前途的药物设计新支架开辟了道路。
By analogy to the structural diversity of covalent bond networks between atoms within organic molecules, one can design topologically diverse peptides from mathematical graphs by assigning amino acids to graph nodes and peptide bonds to graph edges. The key is to use diamino acids or amino diacids as equivalents of trivalent graph nodes, which enables a variety of graph topologies beyond the standard linear and monocyclic graphs in natural peptides. Here the bicyclic decapeptide A(1)FGk(2)VFPE(1)AG(2) (1b) was prepared and crystallized to assign its bridge stereochemistry. The bridge configuration appears as planned by the chirality of the branching amino acids. Bicyclization furthermore depends on the presence of matched chiralities in the branching amino acids. The stereoselective formation of the second bridge opens the way for the synthesis of a large family of bicyclic peptides as promising new scaffolds for drug design.