Graaf Matthew D, Moeller Kevin D
Department of Chemistry, Washington University in St. Louis , St. Louis, Missouri 63130, United States.
J Org Chem. 2016 Feb 19;81(4):1527-34. doi: 10.1021/acs.joc.5b02656. Epub 2016 Jan 28.
The placement of a peptide onto a microelectrode array is frequently complicated by the presence of multiple nucleophiles in the peptide. In the work reported here, we have found that the Chan-Lam coupling reactions used to site-selectively place thiol, alcohol, and amine nucleophiles onto diblock-copolymer-coated surfaces are chemoselective for the placement of thiol and alcohol nucleophiles on the arrays. This means that cysteine- and serine-containing peptides can be placed onto an array without any need to protect the N terminus of the peptide. Furthermore, it was found that placement of thiol groups onto an array with the Chan-Lam reaction using optimized reaction times leads to complete coverage of the electrodes. The extent of this coverage can be controlled by varying the reaction time in a manner that allows for the construction of arrays with a gradient of peptide concentrations.
由于肽中存在多个亲核试剂，将肽放置在微电极阵列上的过程常常变得复杂。在本文报道的工作中，我们发现用于将硫醇、醇和胺亲核试剂位点选择性地放置在双嵌段共聚物涂层表面的Chan-Lam偶联反应，对于硫醇和醇亲核试剂在阵列上的放置具有化学选择性。这意味着含半胱氨酸和丝氨酸的肽可以放置在阵列上，而无需保护肽的N端。此外，还发现使用优化的反应时间通过Chan-Lam反应将硫醇基团放置在阵列上可导致电极完全覆盖。这种覆盖程度可以通过改变反应时间来控制，从而能够构建具有肽浓度梯度的阵列。
