Recently we have reported that the ortho-hydroxy-protected aryl sulfate (OHPAS) system can be exploited as a new self-immolative group (SIG) for phenolic payloads. We extended the system to nonphenolic payloads by simply introducing a para-hydroxy benzyl (PHB) spacer. As an additional variation of the system, we explored a benzylsulfonate version of the OHPAS system and found that it has two distinct breakdown pathways, cyclization and 1,4-elimination, the latter of which implies that para-hydroxy-protected (PHP) benzylsulfonate (BS) can also be used as an alternative SIG. The PHP-BS system was found to be stable chemically and in mouse and human plasma, having payload release rates comparable to those of the original OHPAS conjugates.

中文翻译：

---

磺酸盐版本的OHPAS接头具有两种不同的分解途径：消除途径允许对羟基保护的苄基磺酸盐（PHP-BS）用作替代的自消灭基团。

最近，我们报道了邻羟基保护的硫酸芳基酯（OHPAS）系统可以用作酚类有效载荷的新的自消灭基团（SIG）。通过简单地引入对羟基苄基（PHB）间隔基，我们将系统扩展到了非酚类负载。作为系统的另一个变体，我们探索了OHPSS系统的苄基磺酸盐版本，发现它具有两个不同的分解途径，环化和1,4-消除，后者暗示对羟基保护的（PHP）苄基磺酸盐（BS）也可以用作替代SIG。发现PHP-BS系统在化学上以及在小鼠和人类血浆中均稳定，其有效负载释放速率可与原始OHPAS缀合物相媲美。