[2.2.1]Heterobicyclic Bromovinyl Sulfones for Thiol-Triggered Strategies in Linker Chemistry: Aza- vs Oxa-Norbornadienic Systems

IF 3.9 2区化学 Q1 BIOCHEMICAL RESEARCH METHODS

Bioconjugate Chemistry Pub Date : 2025-08-22 DOI:10.1021/acs.bioconjchem.5c00371

Marina Carranza, Ana T. Carmona*, Celia Maya, Enrique Gil de Montes, Aldrin V. Vasco, Gonçalo J. L. Bernardes and Antonio J. Moreno-Vargas*,

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Abstract

Azanorbornadienes (ANDs) containing a bromovinyl sulfone are able to accept a first thiol and, in a further stage, fragment upon reaction with a second thiol. This fragmentation has been studied in a collection of differently substituted ANDs. The substitution pattern of the AND influences the rate of the first thiolation and, specially, the further fragmentation. N-pyramidalization of selected ANDs was demonstrated via X-ray diffraction. This structural feature attenuates the resonance effect of N-substituents in the further reactivity of ANDs. A comparison with related oxanorbornadienes is also reported. The installation of a fluorogenic AND onto a single domain Antibody against PD-L1 (PD-L1 sdAb) resulted in a conjugate capable of releasing the corresponding fluorogenic pyrrole in the presence of glutathione (GSH) under physiological conditions. Overall, these scaffolds demonstrate potential to be implemented as new drug delivery systems.

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[2.2.1]偶氮偶氮与氧-降冰片二烯体系的偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮偶氮。

含有溴炔基砜的氮杂鸟二烯（and）能够接受第一硫醇，并在进一步的阶段与第二硫醇反应时片断。这种碎片化已经在不同取代基团的集合中进行了研究。AND的取代模式影响第一次硫基化的速率，特别是影响进一步的断裂。通过x射线衍射证实了n -锥体化。这种结构特征减弱了n取代基在手性进一步反应中的共振效应。还报道了与相关的氧生冰片二烯的比较。在抗PD-L1的单域抗体（PD-L1 sdAb）上安装荧光性AND，导致在生理条件下，在谷胱甘肽（GSH）存在下能够释放相应的荧光吡咯的偶联物。总的来说，这些支架显示出作为新的药物输送系统的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bioconjugate Chemistry 生物-化学综合

CiteScore

9.00

自引率

2.10%

发文量

236

审稿时长

1.4 months

期刊介绍： Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.