Development of a novel sulfonate ester-based prodrug strategy

Kengo Hanaya, Shohei Yoshioka, Shinya Ariyasu, Shin Aoki, Mitsuru Shoji, Takeshi Sugai

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

A self-immolative γ-aminopropylsulfonate linker was investigated for use in the development of prodrugs that are reactive to various chemical or biological stimuli. To demonstrate their utility, a leucine-conjugated prodrug of 5-chloroquinolin-8-ol (5-Cl-8-HQ), which is a potent inhibitor against aminopeptidase from Aeromonas proteolytica (AAP), was synthesized. The sulfonate prodrug was considerably stable under physiological conditions, with only enzyme-mediated hydrolysis of leucine triggering the subsequent intramolecular cyclization to simultaneously release 5-Cl-8-HQ and form γ-sultam. It was also confirmed that this γ-aminopropylsulfonate linker was applicable for prodrugs of not only 8-HQ derivatives but also other drugs bearing a phenolic hydroxy group.

Original languageEnglish
JournalBioorganic and Medicinal Chemistry Letters
DOIs
Publication statusAccepted/In press - 2015 Sep 24

Fingerprint

Prodrugs
Esters
Leucine
Bearings (structural)
Cyclization
Hydrolysis
Derivatives
Enzymes
Pharmaceutical Preparations

Keywords

  • Prodrug
  • Protease
  • Suicide substrate
  • Sulfonate
  • Sultam

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Development of a novel sulfonate ester-based prodrug strategy. / Hanaya, Kengo; Yoshioka, Shohei; Ariyasu, Shinya; Aoki, Shin; Shoji, Mitsuru; Sugai, Takeshi.

In: Bioorganic and Medicinal Chemistry Letters, 24.09.2015.

Research output: Contribution to journalArticle

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