Introduction of Para-Hydroxy Benzyl Spacer Greatly Expands the Utility of Ortho-Hydroxy-Protected Aryl Sulfate System: Application to Nonphenolic Payloads

• Published in: Bioconjugate chemistry Vol. 30; no. 7; pp. 1969 - 1978
• Main Authors: Park, Suho, Kim, Sun Young, Cho, Jongun, Jung, Doohwan, Seo, Donghoon, Lee, Jaeho, Lee, Sangkwang, Yun, Sanghyeon, Lee, Hyangsook, Park, Okku, Seo, Beomseok, Kim, Sena, Seol, Minah, Woo, Sung Ho, Park, Tae Kyo
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.07.2019; Amer Chemical Soc
• Subjects: Alcohols - chemical synthesis; Alcohols - chemistry; Amines - chemical synthesis; Amines - chemistry; Aromatic compounds; Benzyl Compounds - chemical synthesis; Benzyl Compounds - chemistry; Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry; Chemistry, Multidisciplinary; Chemistry, Organic; Cyclization; DNA - chemical synthesis; DNA - chemistry; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Life Sciences & Biomedicine; Organic chemistry; Payloads; Phenol - chemical synthesis; Phenol - chemistry; Phenols; Physical Sciences; Plasmas; RNA - chemical synthesis; RNA - chemistry; Science & Technology; Sulfates; Sulfates - chemical synthesis; Sulfates - chemistry; ANTIBODY-DRUG CONJUGATE; RELEASE; PANCRATISTATIN; TRASTUZUMAB EMTANSINE; MITOCHONDRIA; GROWTH
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/acs.bioconjchem.9b00341

The ortho-hydroxy-protected aryl sulfate (OHPAS) linker is composed of a diaryl sulfate backbone equipped with a latent phenol moiety at the ortho position of one of the aryl units. The Ar–OH released when the ortho phenol undergoes intramolecular cyclization and displaces the second aryl unit can be viewed as a payload. We have shown in the preceding paper that the OHPAS linkers are highly stable chemically and in various plasmas, yet release payloads when exposed to suitable triggering conditions. As an extension of the OHPAS system, we employed a para-hydroxy benzyl (PHB) spacer for coupling to nonphenolic payloads; this tactic again provided a highly stable system capable of smooth release of appended payloads. The PHB modification works beautifully for tertiary amine and N-heterocycle payloads.