Foldamers with heterogeneous backbones.
Foldamers with heterogeneous backbones.
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DOI：
10.1021/ar800009n
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发表时间：
2008-10
影响因子：
18.3
通讯作者：
Gellman, Samuel H.
中科院分区：
文献类型：
--
作者：
Horne, W. Seth;Gellman, Samuel H.
由蛋白质和核酸执行的功能为生命提供了基础，化学家们开始询问是否有可能设计出接近这些生物聚合物的结构和功能复杂性的合成低聚物。对具有离散折叠倾向的非天然低聚物折叠体的研究表明，各种合成主链可以显示生物聚合物样构象行为。这一领域的早期工作集中在由单一类型的单体亚基组成的寡聚体上，但最近的努力强调了混合或“异质”主链扩展折叠体的结构和功能库的潜力。在本报告中，我们通过关注含有α-和β-氨基酸残基的例子来说明异质骨架折叠体的前景。使用异质骨架折叠体提供了优于同质骨架对应物的优势，包括基于化学计量和亚基组合模式的变化获得许多新的分子形状，以及改善侧链多样化的前景。最近开发α/β-肽折叠体的努力可以分为两个概念上不同的类别。第一种包括通过“阻断”策略制备的实体，其中α-肽区段和β-肽区段组合以形成杂合寡聚体。第二类包括其中α-和β-氨基酸单体在整个寡聚体序列中以规则模式散布的设计。已经通过这些方法从α/β-肽产生了多种二级结构。α/β-肽的螺旋二级结构最近被转化为更高级的结构，特别是螺旋束四级结构。从α/β-肽折叠体中已经引出了期望的生物学功能。模拟天然存在的宿主防御α-肽的努力已经产生了新的抗菌剂，并导致重新审视关于α-肽和其他两亲性寡聚体之间的结构-活性关系的长期观点。折叠体为模拟参与特定蛋白质-蛋白质识别事件的分子表面提供了新的平台;最近关于参与凋亡信号传导的蛋白质-蛋白质相互作用的α/β-肽抑制剂的成就揭示了基于折叠体的设计的异质主链相对于同质主链的益处。这些在开发具有特定生物活性的α/β-肽方面的初步成功突出了异质骨架折叠体在生物医学应用中的潜力，并为未来新靶点功能的研究提供了指导。
The functions carried out by proteins and nucleic acids provide the foundation for life, and chemists have begun to ask whether it is possible to design synthetic oligomers that approach the structural and functional complexity of these biopolymers. The study of foldamers, non-natural oligomers with discrete folding propensities, has demonstrated that a variety of synthetic backbones can show biopolymer-like conformational behavior. Early work in this area focused on oligomers comprised of a single type of monomer subunit, but recent efforts have highlighted the potential of mixed or “heterogeneous” backbones to expand the structural and functional repertoire of foldamers. In this Account, we illustrate the promise of heterogeneous backbone foldamers by focusing on examples containing both α- and β-amino acid residues. The use of heterogeneous backbone foldamers offers advantages over homogeneous backbone counterparts, including access to many new molecular shapes, based on variations in the stoichiometries and patterns of subunit combination, and improved prospects for side chain diversification. Recent efforts to develop α/β-peptide foldamers can be divided into two conceptually distinct classes. The first includes entities prepared by a “block” strategy, in which α-peptide segments and β-peptide segments are combined to form a hybrid oligomer. The second class encompasses designs in which α- and β-amino acid monomers are interspersed in a regular pattern throughout an oligomer sequence. A variety of secondary structures has been generated from α/β-peptides via these approaches. Helical secondary structures available to α/β-peptides have recently been parlayed into higher order structure, specifically, helix bundle quaternary structure. Desirable biological functions have been elicited from α/β-peptide foldamers. Efforts to mimic naturally occurring host-defense α-peptides have yielded new antimicrobial agents and led to a re-examination of the long-held views regarding structure-activity relationships among α-peptides and other amphiphilic oligomers. Foldamers offer new platforms for mimicry of molecular surfaces involved in specific protein-protein recognition events; recent achievements with α/β-peptide inhibitors of protein-protein interactions involved in apoptotic signaling have revealed benefits of heterogeneous backbones relative to homogeneous backbones for foldamer-based designs. These initial successes in the development of α/β-peptides with specific biological activities highlight the potential of heterogeneous backbone foldamers for biomedical applications and provide guidelines for the future work on new target functions.
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影响因子：
2.9
作者：
Baldauf, Carsten;Guenther, Robert;Hofmann, Hans-Jorg
通讯作者：
Hofmann, Hans-Jorg
影响因子：
16.6
作者：
De Pol, S;Zorn, C;Reiser, O
通讯作者：
Reiser, O
影响因子：
4.9
作者：
Jagadeesh, Bharatam;Prabhakar, Anabathula;Jagannadh, Bulusu
通讯作者：
Jagannadh, Bulusu
DOI：
10.1073/pnas.0701297104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Czabotar, Peter E.;Lee, Erinna F.;Colman, Peter M.
通讯作者：
Colman, Peter M.
影响因子：
56.9
作者：
HARBURY, PB;ZHANG, T;ALBER, T
通讯作者：
ALBER, T