Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors

Kyeong Lee; Shanthaveerappa K. Boovanahalli; Ky Youb Nam; Sang Uk Kang; Mijeoung Lee; Jason Phan; Li Wu; David S. Waugh; Zhong Yin Zhang; Tai No Kyoung; Jun Lee Jung; Terrence R. Burke

doi:10.1016/j.bmcl.2005.06.027

Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors

Kyeong Lee, Shanthaveerappa K. Boovanahalli, Ky Youb Nam, Sang Uk Kang, Mijeoung Lee, Jason Phan, Li Wu, David S. Waugh, Zhong Yin Zhang, Tai No Kyoung, Jun Lee Jung, Terrence R. Burke

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

We report the synthesis of a series of monoanionic phosphotyrosyl (pTyr) mimetic-containing tripeptides based on 'Fmoc-Glu(OBn)-Xxx-Leu-amide' (where Xxx = pTyr mimetic) and their N-terminally modified derivatives. The inhibitory potencies of compounds were tested against YopH and human PTP1B enzymes. Several compounds exhibited noteworthy activity against both YopH and PTP1B. Among the N-terminally modified analogues, 5-methylindole derivative 30 was found to be the best moiety to replace base-labile Fmoc group. A mode of binding with YopH is proposed for tripeptides 21, 30, and 31.

Original language	English
Pages (from-to)	4037-4042
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	18
DOIs	https://doi.org/10.1016/j.bmcl.2005.06.027
Publication status	Published - 2005 Sep 15

Bibliographical note

Funding Information:
L.W. and Z.-Y.Z. were supported by National Institute of Health Grant 1U54 AI57158. We thank Dr. Shinya Oishi for help in HPLC purifications.

All Science Journal Classification (ASJC) codes

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

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10.1016/j.bmcl.2005.06.027

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title = "Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors",

abstract = "We report the synthesis of a series of monoanionic phosphotyrosyl (pTyr) mimetic-containing tripeptides based on 'Fmoc-Glu(OBn)-Xxx-Leu-amide' (where Xxx = pTyr mimetic) and their N-terminally modified derivatives. The inhibitory potencies of compounds were tested against YopH and human PTP1B enzymes. Several compounds exhibited noteworthy activity against both YopH and PTP1B. Among the N-terminally modified analogues, 5-methylindole derivative 30 was found to be the best moiety to replace base-labile Fmoc group. A mode of binding with YopH is proposed for tripeptides 21, 30, and 31.",

author = "Kyeong Lee and Boovanahalli, {Shanthaveerappa K.} and Nam, {Ky Youb} and Kang, {Sang Uk} and Mijeoung Lee and Jason Phan and Li Wu and Waugh, {David S.} and Zhang, {Zhong Yin} and Kyoung, {Tai No} and Jung, {Jun Lee} and Burke, {Terrence R.}",

note = "Funding Information: L.W. and Z.-Y.Z. were supported by National Institute of Health Grant 1U54 AI57158. We thank Dr. Shinya Oishi for help in HPLC purifications.",

year = "2005",

month = sep,

day = "15",

doi = "10.1016/j.bmcl.2005.06.027",

language = "English",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors

AU - Lee, Kyeong

AU - Boovanahalli, Shanthaveerappa K.

AU - Nam, Ky Youb

AU - Kang, Sang Uk

AU - Lee, Mijeoung

AU - Phan, Jason

AU - Wu, Li

AU - Waugh, David S.

AU - Zhang, Zhong Yin

AU - Kyoung, Tai No

AU - Jung, Jun Lee

AU - Burke, Terrence R.

N1 - Funding Information: L.W. and Z.-Y.Z. were supported by National Institute of Health Grant 1U54 AI57158. We thank Dr. Shinya Oishi for help in HPLC purifications.

PY - 2005/9/15

Y1 - 2005/9/15

N2 - We report the synthesis of a series of monoanionic phosphotyrosyl (pTyr) mimetic-containing tripeptides based on 'Fmoc-Glu(OBn)-Xxx-Leu-amide' (where Xxx = pTyr mimetic) and their N-terminally modified derivatives. The inhibitory potencies of compounds were tested against YopH and human PTP1B enzymes. Several compounds exhibited noteworthy activity against both YopH and PTP1B. Among the N-terminally modified analogues, 5-methylindole derivative 30 was found to be the best moiety to replace base-labile Fmoc group. A mode of binding with YopH is proposed for tripeptides 21, 30, and 31.

AB - We report the synthesis of a series of monoanionic phosphotyrosyl (pTyr) mimetic-containing tripeptides based on 'Fmoc-Glu(OBn)-Xxx-Leu-amide' (where Xxx = pTyr mimetic) and their N-terminally modified derivatives. The inhibitory potencies of compounds were tested against YopH and human PTP1B enzymes. Several compounds exhibited noteworthy activity against both YopH and PTP1B. Among the N-terminally modified analogues, 5-methylindole derivative 30 was found to be the best moiety to replace base-labile Fmoc group. A mode of binding with YopH is proposed for tripeptides 21, 30, and 31.

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EP - 4042

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 18

ER -

Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

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