Acylsulfonamide-containing PTP1B inhibitors designed to mimic an enzyme-bound water of hydration

Ding Guo Liu, Yang Gao, Johannes H. Voigt, Kyeong Lee, Marc C. Nicklaus, Li Wu, Zhong-Yin Zhang, Terrence R. Burke

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Previously, it had been reported that 6-(phosphonodifluoromethyl)-2-naphthoic acid binds to the protein-tyrosine phosphatase PTP1B with its 2-carboxyl group interacting only indirectly through a bridging water molecule. Reported herein is a family of new analogues that utilize acylsulfonamido functionality both to mimic this water of hydration and to provide an additional new site for elaboration not found in the parent carboxyl-containing analogue. Target acylsulfonamides were prepared in two steps from commercially available primary sulfonamides, which were selected based on in silico screening for their potential ability to interact with one of three binding surfaces proximal to the PTP1B catalytic site. In general, modest potency enhancements were observed. Arylacylsulfonamides represent a structure-based extension of inhibitor design that may have broader utility in the development of PTP1B inhibitors.

Original languageEnglish (US)
Pages (from-to)3005-3007
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume13
Issue number18
DOIs
StatePublished - Sep 2003
Externally publishedYes

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Hydration
Protein Tyrosine Phosphatases
Water
Sulfonamides
Enzymes
Computer Simulation
Catalytic Domain
Screening
Molecules
2-naphthoic acid

ASJC Scopus subject areas

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

Cite this

Acylsulfonamide-containing PTP1B inhibitors designed to mimic an enzyme-bound water of hydration. / Liu, Ding Guo; Gao, Yang; Voigt, Johannes H.; Lee, Kyeong; Nicklaus, Marc C.; Wu, Li; Zhang, Zhong-Yin; Burke, Terrence R.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 13, No. 18, 09.2003, p. 3005-3007.

Research output: Contribution to journalArticle

Liu, Ding Guo ; Gao, Yang ; Voigt, Johannes H. ; Lee, Kyeong ; Nicklaus, Marc C. ; Wu, Li ; Zhang, Zhong-Yin ; Burke, Terrence R. / Acylsulfonamide-containing PTP1B inhibitors designed to mimic an enzyme-bound water of hydration. In: Bioorganic and Medicinal Chemistry Letters. 2003 ; Vol. 13, No. 18. pp. 3005-3007.
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AU - Wu, Li

AU - Zhang, Zhong-Yin

AU - Burke, Terrence R.

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