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

Department of Pharmacy

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

22 Scopus citations

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
State	Published - 15 Sep 2005

Keywords

Bioterrorism
PTP1B
pTyr mimetics
Tripeptides
YopH

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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.",

keywords = "Bioterrorism, PTP1B, pTyr mimetics, Tripeptides, YopH",

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.}",

year = "2005",

month = sep,

day = "15",

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

language = "English",

volume = "15",

pages = "4037--4042",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "18",

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TY - JOUR

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.

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.

KW - Bioterrorism

KW - PTP1B

KW - pTyr mimetics

KW - Tripeptides

KW - YopH

UR - http://www.scopus.com/inward/record.url?scp=23644432990&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2005.06.027

DO - 10.1016/j.bmcl.2005.06.027

M3 - Article

C2 - 16039123

AN - SCOPUS:23644432990

SN - 0960-894X

VL - 15

SP - 4037

EP - 4042

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 18

ER -

Synthesis of tripeptides as potent Yersinia protein tyrosine phosphatase inhibitors

Abstract

Keywords

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