Surprisingly stable helical conformations in α/β-peptides by incorporation of cis-β-aminocyclopropane carboxylic acids
Surprisingly stable helical conformations in α/β-peptides by incorporation of cis-β-aminocyclopropane carboxylic acids
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DOI：
10.1002/anie.200352267
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发表时间：
2004-01-01
影响因子：
16.6
通讯作者：
Reiser, O
中科院分区：
文献类型：
--
作者：
De Pol, S;Zorn, C;Reiser, O
结构定义的多肽单元的开发是蛋白质设计的重要前提。因此，寻找在溶液中具有稳定构象的寡肽，即所谓的折叠体，[1]是生物有机化学的一个活跃领域。大多数折叠体是同源寡肽，但也有一些包含两个或多个不同残基的折叠体的例子被报道。[2]由自然产生的α氨基酸构建的多肽通常必须至少有12个单位的长度，才能在溶液中采用稳定的构象。相反，由β-氨基酸组成的寡肽即使在5到8个单位的短低聚物中也具有令人惊讶的稳定的二级结构。[3]主要由α-氨基酸组成的环肽中β-氨基酸的转折结构的稳定性也被认识到。[4]我们最近可以表明，交替的α氨基酸和顺式-β-氨基环丙烷羧酸(cis-β-AcCs)[5]可以产生令人惊讶的短的无环α/β肽，其选择性地与神经肽Y的Y1受体结合并且具有高亲和力。[6]为了深入了解α/β-肽是否形成特别稳定的二级结构，我们研究了由(L)-丙氨酸7和顺-β-氨基环丙烷羧酸的任一对映体，即8和Et-8组成的寡肽1-6(方案1)。
The development of structurally defined peptide units is an important prerequisite for protein design. The search for oligopeptides having stable conformations in solution, socalled foldamers,[1] is therefore an active area of bioorganic chemistry. Most foldamers are homooligopeptides, but some examples of foldamers containing two or more different residues have been also reported.[2] Peptides constructed from the naturally occurring αamino acids must typically have a length of at least 12 units in order to adopt a stable conformation in solution. In contrast, oligopeptides composed of β-amino acids assume surprisingly stable secondary structures even in short oligomers of five to eight units.[3] The stabilization of turn structures in cyclic peptides composed of mainly α-amino acids by incorporation of β-amino acids has also been recognized.[4]We could recently show that alternating αamino acids with cis-β-aminocyclopropanecarboxylic acids (cis-β-ACCs)[5] resulted in surprisingly short acyclic α/βpeptides that bind selectively and with high affinity to the Y1 receptor of neuropeptide Y.[6] In order to gain insight on whether α/β-peptides form especially stable secondary structures, we investigated oligopeptides 1–6, which consist of (L)-alanine 7 and either enantiomer of cis-β-aminocyclopropanecarboxylic acid, that is, 8 and ent-8 (Scheme 1).[7] Here, we