Bindra V A, Kuki A
Department of Chemistry, Baker Laboratory, Cornell University, Ithaca, New York, USA.
Int J Pept Protein Res. 1994 Dec;44(6):539-48. doi: 10.1111/j.1399-3011.1994.tb01142.x.
Two sterically constrained peptides [iBoc-Aib-Aib-Aib-DkNap-Leu-Qx-Ala-Aib-Aib-Fl, (Dk4Qx6[7/9]) and iBoc-Aib-Aib-Aib-DkNap-Leu-Aib-Ala-Aib-Aib-Fl, (Dk4[7/9])] containing alpha-aminoisobutyric acid (Aib) and Aib-class amino acids in conjunction with selected mono-alpha-alkyl amino acids were synthesized by an optimized TBTU/HOBt procedure. The use of Aib-class amino acids (e.g. DkNap and Qx), defined and discussed here, gives rise to the same overwhelmingly 3(10)-helical backbone conformation as that provided by simpler Aib-rich peptides and homopeptides. The synthetic alpha,alpha-dialkylamino acids (DkNap, Qx) are aromatic homologues of the known alicyclic variants of Aib, the Ac5c and Ac6c amino acids. Two new organic solubilizing groups for peptides, iBoc and 2-methoxyethylamine, are introduced. The 1H nuclear magnetic resonance analyses of the Dk4[7/9] and Dk4Qx6[7/9] peptides demonstrate the unambiguous 3(10)-helical hydrogen bonding pattern of these peptides, confirming the design objective of these sequence patterns containing greater than 50% Aib and Aib-class composition.
通过优化的TBTU/HOBt方法合成了两种空间受限肽[iBoc-Aib-Aib-Aib-DkNap-Leu-Qx-Ala-Aib-Aib-Fl，(Dk4Qx6[7/9])和iBoc-Aib-Aib-Aib-DkNap-Leu-Aib-Ala-Aib-Aib-Fl，(Dk4[7/9])]，它们含有α-氨基异丁酸(Aib)和Aib类氨基酸，并结合了选定的单α-烷基氨基酸。本文定义和讨论的Aib类氨基酸(如DkNap和Qx)的使用，产生了与更简单的富含Aib的肽和同肽所提供的相同的压倒性的3(10)-螺旋主链构象。合成的α,α-二烷基氨基酸(DkNap, Qx)是已知的Aib的脂环族变体Ac5c和Ac6c氨基酸的芳香同系物。引入了两种用于肽的新型有机增溶基团，即iBoc和2-甲氧基乙胺。Dk4[7/9]和Dk4Qx6[7/9]肽的1H核磁共振分析表明了这些肽明确的3(10)-螺旋氢键模式，证实了这些含有超过50% Aib和Aib类组成的序列模式的设计目标。
