Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis

Arwin J. Brouwer; Ronald C. Elgersma; Monika Jagodzinska; Dirk T.S. Rijkers; Rob M.J. Liskamp

doi:10.1016/j.bmcl.2007.11.009

Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis

Arwin J. Brouwer, Ronald C. Elgersma, Monika Jagodzinska, Dirk T.S. Rijkers, Rob M.J. Liskamp

Department of Medicinal Chemistry and Chemical Biology

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

Abstract

The synthesis of a new peptidomimetic structure, the alkene dipeptidosulfonamide isostere, is described. The synthesis is based on a cross metathesis reaction between two allylic building blocks, both in solution and on the solid phase. This method was also applicable to the solid phase synthesis of alkene dipeptide isosteres. Derivatives of amylin(20-29) containing the alkene dipeptidosulfonamide isostere as well as the alkene dipeptide isostere were successfully synthesized using the solid phase cross metathesis method. Investigation of relations between structure and fibril formation of these amylin(20-29) derivatives showed retardation of fibril formation and altered secondary structures, compared to native amylin(20-29). © 2007 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	78-84
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2007.11.009
Publication status	Published - 1 Jan 2008

Keywords

Alkenedipeptide isosteres
Alkenedipeptidosulfonamide isosteres
Amyloid
Peptidomimetics
Solid phase cross metathesis
alkene
amylin
dipeptide
dipeptidosulfonamide
sulfonamide
unclassified drug
article
chemical structure
circular dichroism
electrospray mass spectrometry
enzymatic degradation
fiber
peptide synthesis
solid phase synthesis
transmission electron microscopy
Wittig reaction

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10.1016/j.bmcl.2007.11.009

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@article{59755b28f6904204bc06009dba03db3e,

title = "Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis",

abstract = "The synthesis of a new peptidomimetic structure, the alkene dipeptidosulfonamide isostere, is described. The synthesis is based on a cross metathesis reaction between two allylic building blocks, both in solution and on the solid phase. This method was also applicable to the solid phase synthesis of alkene dipeptide isosteres. Derivatives of amylin(20-29) containing the alkene dipeptidosulfonamide isostere as well as the alkene dipeptide isostere were successfully synthesized using the solid phase cross metathesis method. Investigation of relations between structure and fibril formation of these amylin(20-29) derivatives showed retardation of fibril formation and altered secondary structures, compared to native amylin(20-29). {\textcopyright} 2007 Elsevier Ltd. All rights reserved.",

keywords = "Alkenedipeptide isosteres, Alkenedipeptidosulfonamide isosteres, Amyloid, Peptidomimetics, Solid phase cross metathesis, alkene, amylin, dipeptide, dipeptidosulfonamide, sulfonamide, unclassified drug, article, chemical structure, circular dichroism, electrospray mass spectrometry, enzymatic degradation, fiber, peptide synthesis, solid phase synthesis, transmission electron microscopy, Wittig reaction",

author = "Brouwer, {Arwin J.} and Elgersma, {Ronald C.} and Monika Jagodzinska and Rijkers, {Dirk T.S.} and Liskamp, {Rob M.J.}",

year = "2008",

month = jan,

day = "1",

doi = "10.1016/j.bmcl.2007.11.009",

language = "English",

volume = "18",

pages = "78--84",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "1",

}

Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis. / Brouwer, Arwin J.; Elgersma, Ronald C.; Jagodzinska, Monika et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 18, No. 1, 01.01.2008, p. 78-84.

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

TY - JOUR

T1 - Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis

AU - Brouwer, Arwin J.

AU - Elgersma, Ronald C.

AU - Jagodzinska, Monika

AU - Rijkers, Dirk T.S.

AU - Liskamp, Rob M.J.

PY - 2008/1/1

Y1 - 2008/1/1

N2 - The synthesis of a new peptidomimetic structure, the alkene dipeptidosulfonamide isostere, is described. The synthesis is based on a cross metathesis reaction between two allylic building blocks, both in solution and on the solid phase. This method was also applicable to the solid phase synthesis of alkene dipeptide isosteres. Derivatives of amylin(20-29) containing the alkene dipeptidosulfonamide isostere as well as the alkene dipeptide isostere were successfully synthesized using the solid phase cross metathesis method. Investigation of relations between structure and fibril formation of these amylin(20-29) derivatives showed retardation of fibril formation and altered secondary structures, compared to native amylin(20-29). © 2007 Elsevier Ltd. All rights reserved.

AB - The synthesis of a new peptidomimetic structure, the alkene dipeptidosulfonamide isostere, is described. The synthesis is based on a cross metathesis reaction between two allylic building blocks, both in solution and on the solid phase. This method was also applicable to the solid phase synthesis of alkene dipeptide isosteres. Derivatives of amylin(20-29) containing the alkene dipeptidosulfonamide isostere as well as the alkene dipeptide isostere were successfully synthesized using the solid phase cross metathesis method. Investigation of relations between structure and fibril formation of these amylin(20-29) derivatives showed retardation of fibril formation and altered secondary structures, compared to native amylin(20-29). © 2007 Elsevier Ltd. All rights reserved.

KW - Alkenedipeptide isosteres

KW - Alkenedipeptidosulfonamide isosteres

KW - Amyloid

KW - Peptidomimetics

KW - Solid phase cross metathesis

KW - alkene

KW - amylin

KW - dipeptide

KW - dipeptidosulfonamide

KW - sulfonamide

KW - unclassified drug

KW - article

KW - chemical structure

KW - circular dichroism

KW - electrospray mass spectrometry

KW - enzymatic degradation

KW - fiber

KW - peptide synthesis

KW - solid phase synthesis

KW - transmission electron microscopy

KW - Wittig reaction

U2 - 10.1016/j.bmcl.2007.11.009

DO - 10.1016/j.bmcl.2007.11.009

M3 - Article

SN - 0960-894X

VL - 18

SP - 78

EP - 84

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 1

ER -

Delayed fibril formation of amylin(20-29) by incorporation of alkene dipeptidosulfonamide isosteres obtained by solid phase olefin cross metathesis

Abstract

Keywords

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