Sharma Gangavaram V M, Babu Bommagani Shoban, Ramakrishna Kallaganti V S, Nagendar Pendem, Kunwar Ajit C, Schramm Peter, Baldauf Carsten, Hofmann Hans-Jörg
Discovery Laboratory, Organic Chemistry Division III, Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Chemistry. 2009;15(22):5552-66. doi: 10.1002/chem.200802078.
Stimulated by an overview on all periodic folding patterns of alpha/delta-hybrid peptides with 1:1 alternating backbone provided by ab initio molecular orbital theory, the first representatives of this foldamer class were synthesized connecting novel C-linked carbo-delta-amino acid constituents and L-Ala. In agreement with theoretical predictions, extensive NMR spectroscopic analyses confirm the formation of new motifs of 13/11-mixed helical patterns in these peptides supported by the rigidity of the D-xylose side chain in the selected delta-amino acid constituents. Relationships between possible helix types in alpha/delta-hybrid peptides and their counterparts in other 1:1 hybrid peptide classes and native alpha-peptides are discussed; these indicate the high potential of these foldamers to mimic native peptide secondary structures. The design of alpha/delta-hybrid peptides provides an opportunity to expand the domain of foldamers and allows the introduction of desired functionalities through the alpha-amino acid constituents.
受从头算分子轨道理论提供的关于具有1:1交替主链的α/δ杂合肽所有周期性折叠模式的综述的启发，合成了这类折叠体的首批代表物，它们连接了新型C-连接的碳-δ-氨基酸成分和L-丙氨酸。与理论预测一致，广泛的核磁共振光谱分析证实，在这些肽中形成了新的13/11混合螺旋模式基序，所选δ-氨基酸成分中的D-木糖侧链的刚性对此起到了支持作用。讨论了α/δ杂合肽中可能的螺旋类型与其在其他1:1杂合肽类和天然α-肽中的对应物之间的关系；这些关系表明这些折叠体在模拟天然肽二级结构方面具有很高的潜力。α/δ杂合肽的设计为扩展折叠体领域提供了机会，并允许通过α-氨基酸成分引入所需的功能。
