Laboratory of Structural Chemistry and Biology, Institute of Chemistry, ELTE Eötvös Loránd University, Pázmány P. Stny. 1/A, Budapest, 1117, Hungary.
MTA-ELTE Protein Modeling Research Group, Pázmány P. Sétány. 1/A, Budapest, 1117, Hungary.
Amino Acids. 2019 Apr;51(4):669-678. doi: 10.1007/s00726-019-02702-9. Epub 2019 Feb 13.
The synthesis of α/β-chimeras comprises peptide bond formation from α- to β-, from β- to β-, and from β- to α-amino acid residues. The fine-tuned solid phase synthesis of -GXXG- chimera peptides containing the simplest achiral α-amino acid glycine and two cyclic SAAs of different ring size [X denoting cyclic β-Sugar Amino Acids (β-SAA)] is reported, variants containing Fmoc-RibAFU(ip)-OH a furanoid-, and Fmoc-GlcAPU(Me)-OH a pyranoid-type structural "Lego-element". Systematic search for the best coupling strategy with both H-β-SAA-OHs is described, including the comparison of the different coupling reagents and conditions. Selecting the optimal reagent (from commonly used PyBOP, HATU and HOBt) was assisted by time-resolved H-NMR: formation and stability of the Fmoc protected active esters were compared. We found that PyBOP is the best choice for successfully coupling both H-β-SAA-OH prototypes. The present comparative results open a reasonable route for building efficiently various -β-SAA- containing homo- and heterooligomers.
α/β-嵌合体的合成包括从α-到β-、从β-到β-和从β-到α-氨基酸残基的肽键形成。报道了含有最简单的非手性α-氨基酸甘氨酸和两个不同环大小的环状 SAA [X 表示环状β-糖氨基酸（β-SAA）]的 -GXXG-嵌合肽的精细调节固相合成，变体含有 Fmoc-RibAFU(ip)-OH 的呋喃型和 Fmoc-GlcAPU(Me)-OH 的吡喃型结构“乐高元件”。描述了与两种 H-β-SAA-OH 一起进行最佳偶联策略的系统搜索，包括比较不同的偶联试剂和条件。通过时间分辨 H-NMR 辅助选择最佳试剂（从常用的 PyBOP、HATU 和 HOBt 中选择）：比较了 Fmoc 保护的活性酯的形成和稳定性。我们发现 PyBOP 是成功偶联两种 H-β-SAA-OH 原型的最佳选择。目前的比较结果为有效地构建各种含有β-SAA 的同聚体和杂聚体提供了合理的途径。
