Effects of chirality and side chain length in Cα,α-dialkylated residues on β-hairpin peptide folded structure and stability.
Effects of chirality and side chain length in Cα,α-dialkylated residues on β-hairpin peptide folded structure and stability.
复制标题
Cα,α-二烷基化残基的手性和侧链长度对β-发夹肽折叠结构和稳定性的影响。
DOI：
10.1039/d3ob00963g
复制
发表时间：
2023
影响因子：
3.2
通讯作者：
Lengyel,GeorgeA
中科院分区：
文献类型：
--
作者：
Heath,ShelbyL;Horne,WSeth;Lengyel,GeorgeA
将具有大取代基的非手性Cα，α-二烷基化氨基酸策略性地掺入肽中可用于促进延伸链构象并抑制与淀粉样蛋白形成相关的蛋白质-蛋白质相互作用。在这项工作中，我们评估的热力学影响的手性Cα，α单体的折叠偏好在这样的系统中，通过引入一系列的Cα-甲基化和Cα-乙基化的残基到一个β-发夹主机序列。根据人工单体的立体化学构型和额外疏水填充的可能性，Cα-乙基-C α-丙基甘氨酸残基可以提供相对于非手性Cα，α-二乙基类似物相似或增强的折叠稳定性。
Strategic incorporation of achiral Cα,α-dialkylated amino acids with bulky substituents into peptides can be used to promote extended strand conformations and inhibit protein–protein interactions associated with amyloid formation. In this work, we evaluate the thermodynamic impact of chiral Cα,α monomers on folding preferences in such systems through introduction of a series of Cα-methylated and Cα-ethylated residues into a β-hairpin host sequence. Depending on stereochemical configuration of the artificial monomer and potential for additional hydrophobic packing, a Cα-ethyl-Cα-propyl glycine residue can provide similar or enhanced folded stability relative to an achiral Cα,α-diethyl analogue.