On-resin N-formylation of peptides: a head-to-head comparison of reagents in solid-phase synthesis of ligands for formyl peptide receptors
On-resin N-formylation of peptides: a head-to-head comparison of reagents in solid-phase synthesis of ligands for formyl peptide receptors
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DOI：
10.1002/psc.2998
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发表时间：
2017-05-01
影响因子：
2.1
通讯作者：
Franzyk，Henrik
中科院分区：
文献类型：
--
作者：
Christensen，Simon Bendt;Hansen，Anna Mette;Franzyk，Henrik
通过筛选多种包含脂肪族甲酸酯（甲酸乙酯、甲酸2,2,2-三氟乙酯和甲酸氰甲酯）、芳香族酯（甲酸苯酯和甲酸对硝基苯酯）和N-甲酰基咪唑的试剂，并用偶联剂1-乙基-3-(3-二甲基氨基丙基)原位活化甲酸，确定了肽在树脂上有效N-甲酰化的一般条件。碳二亚胺。最初，检查了短模型肽甲酰化的反应时间和溶剂的影响。通过在一系列较长甲酰基肽配体的合成中使用不同的接头和固体支持物，进一步检查了最有效的试剂。对于甲酸对硝基苯酯和 N-甲酰咪唑，在 2 小时内几乎达到完全转化，尽管通过不同连接体连接到 Tentagel 树脂上的较长肽需要延长反应时间。总体而言，市售的活化甲酸对硝基苯酯被证明是最方便和通用的，因为在室温下 1-3 小时后即可获得高甲酰化度，而传统或微波辅助加热可将甲酰化时间缩短至 20 分钟。版权所有© 2017 欧洲肽协会和 John Wiley & Sons, Ltd.
General conditions for efficient on-resin N-formylation of peptides were identified by screening of a number of reagents comprising aliphatic formates (ethyl formate, 2, 2, 2-trifluoroethyl formate, and cyanomethyl formate), aromatic esters (phenyl formate and p-nitrophenyl formate), and N-formylimidazole and in situ activation of formic acid with the coupling reagent 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. Initially, reaction time and influence of solvent were examined for the formylation of a short model peptide. The most efficient reagents were examined further by using different linkers and solid supports in the synthesis of an array of longer formyl peptide ligands. For p-nitrophenyl formate and N-formylimidazole, almost complete conversion was reached within 2 h, albeit longer peptides attached to Tentagel resins via different linkers required an extended reaction time. Overall, the commercially available activated ester p-nitrophenyl formate proved to be most convenient and versatile as high formylation degrees were obtained after 1–3 h at room temperature, while either conventional or microwaveassisted heating allowed reduction of the formylation time to 20 min. Copyright© 2017 European Peptide Society and John Wiley & Sons, Ltd.