Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa.
Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban 4001, South Africa; KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa.
Bioorg Chem. 2020 Nov;104:104334. doi: 10.1016/j.bioorg.2020.104334. Epub 2020 Oct 6.
In the field of bioconjugation, linker development has witnessed massive growth in recent years. 2,4,6-Trichloro-1,3,5-triazine (TCT) is a tridentate linker that can accommodate three distinct nucleophiles. Herein, the reaction of azido triazine derivatives with nucleophiles (amine, thiol and phenol) is studied. The replacement of first chlorine was performed at 0 °C while that of the last chlorine was achieved successfully at rt. As a proof of concept of this strategy with potential application in biological studies, pentapeptides (Ac-XGGFL-NH where X = Lys or Tyr or Cys) were reacted with 2-azido-4,6-dichlorotriazine to replace the first and second chlorine at 0 °C and at rt, respectively. The reactivity of 2-azido-4,6-dichlorotriazine was found to be similar for the α and ε amine group present in same peptide. These findings demonstrate the applicability of 2-azido-4,6-dichlorotriazine as a linker with potential further application in bioconjugation.
在生物偶联领域，连接子的发展近年来取得了巨大的增长。2,4,6-三氯-1,3,5-三嗪（TCT）是一种三齿连接子，可以容纳三个不同的亲核试剂。本文研究了叠氮三嗪衍生物与亲核试剂（胺、巯基和酚）的反应。首先氯的取代反应在 0°C 进行，而最后一个氯的取代反应则在室温下成功进行。作为该策略在生物研究中具有潜在应用的概念验证，五肽（Ac-XGGFL-NH，其中 X=赖氨酸或酪氨酸或半胱氨酸）与 2-叠氮-4,6-二氯三嗪反应，分别在 0°C 和室温下取代第一和第二个氯。发现 2-叠氮-4,6-二氯三嗪对同一肽中存在的α和ε胺基具有相似的反应性。这些发现证明了 2-叠氮-4,6-二氯三嗪作为连接子的适用性，并有进一步在生物偶联中的应用潜力。
