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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@article{8efc018ebd0a4959b39dd28c6e482484,

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",

}

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 - https://www.scopus.com/pages/publications/23644432990

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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