Synthesis of peptide macrocycles using unprotected amino aldehydes
Synthesis of peptide macrocycles using unprotected amino aldehydes
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DOI：
10.1038/nprot.2010.127
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发表时间：
2010-01-01
期刊：
影响因子：
14.8
通讯作者：
Yudin, Andrei K.
中科院分区：
文献类型：
--
作者：
Rotstein, Benjamin H.;Rai, Vishal;Yudin, Andrei K.
该方案描述了从线性肽前体、异腈和氮丙啶醛合成肽大环化合物的方法。讨论了反应组分对反应效率的影响。大环化通过制备九元环肽大环来举例说明。该产物通过用荧光硫醇亲核打开氮丙啶环进一步官能化。这种转化构成了大环肽分子的有用的后期官能化。实验部分描述了所需起始物料的选择以及代表性氮丙啶-2-甲醛二聚体的制备。肽大环化合物的合成和分离可在6 h内完成，开环约需6-8 h。氮丙啶-2-甲醛试剂可商购获得或可由容易获得的起始材料在约4天内合成。所描述的策略不限于代表性合成中使用的特定肽、异氰化物、氮丙啶醛或亲核试剂。
This protocol describes a method for synthesizing peptide macrocycles from linear peptide precursors, isocyanides and aziridine aldehydes. The effects of the reaction components on the efficiency of the process are discussed. Macrocyclization is exemplified by the preparation of a nine-membered ring peptide macrocycle. The product is further functionalized by nucleophilic opening of the aziridine ring with a fluorescent thiol. This transformation constitutes a useful late-stage functionalization of a macrocyclic peptide molecule. The experimental section describes the selection of the required starting materials, and the preparation of a representative aziridine-2-carboxaldehyde dimer. The synthesis and isolation of the peptide macrocycle can be accomplished in 6 h, and the ring-opening requires approximately 6-8 h. The aziridine-2-carboxaldehyde reagent is commercially available or can be synthesized from readily available starting materials in approximately 4 d. The strategy described is not limited to the specific peptide, isocyanide, aziridine aldehyde or nucleophile used in the representative synthesis.