Structural determinants of the selectivity of KTS-disintegrins for the α1β1 integrin

Dariusz G. Kisiel; Juan J. Calvete; Jehoshua Katzhendler; Andrzej Fertala; Philip Lazarovici; Cezary Marcinkiewicz

doi:10.1016/j.febslet.2004.10.050

Structural determinants of the selectivity of KTS-disintegrins for the α1β1 integrin

Dariusz G. Kisiel, Juan J. Calvete, Jehoshua Katzhendler, Andrzej Fertala, Philip Lazarovici, Cezary Marcinkiewicz^*

^*Corresponding author for this work

School of Pharmacy

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

63 Scopus citations

Abstract

KTS-disintegrins are a subfamily of short monomeric disintegrins that are potent and selective inhibitors of α1β1 integrin. The amino acid sequence of the new KTS-disintegrin, viperistatin, differs from previously characterized obtustatin in three residues at position 24 (within the integrin binding loop), 38 (hydrophobic core) and 40 (C-terminal region). Noteworthy, viperistatin is about 25-fold more potent than obtustatin inhibiting the binding of this integrin to collagen IV. Synthetic peptides representing the full-length of integrin-binding loops of these disintegrins showed that the Leu24/Arg substitution appears to be partly responsible for the increased inhibitory activity of viperistatin over obtustatin.

Original language	English
Pages (from-to)	478-482
Number of pages	5
Journal	FEBS Letters
Volume	577
Issue number	3
DOIs	https://doi.org/10.1016/j.febslet.2004.10.050
State	Published - 19 Nov 2004

Keywords

BSA, bovine serum albumin
CMFDA, 5-chloromethylfluorescein diacetate
HPLC, high-performance liquid chromatography
MALDI-TOF, matrix-assisted laser-desorption ionization time-of-flight mass spectrometry
TFA, trifluoroacetic acid

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10.1016/j.febslet.2004.10.050

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title = "Structural determinants of the selectivity of KTS-disintegrins for the α1β1 integrin",

abstract = "KTS-disintegrins are a subfamily of short monomeric disintegrins that are potent and selective inhibitors of α1β1 integrin. The amino acid sequence of the new KTS-disintegrin, viperistatin, differs from previously characterized obtustatin in three residues at position 24 (within the integrin binding loop), 38 (hydrophobic core) and 40 (C-terminal region). Noteworthy, viperistatin is about 25-fold more potent than obtustatin inhibiting the binding of this integrin to collagen IV. Synthetic peptides representing the full-length of integrin-binding loops of these disintegrins showed that the Leu24/Arg substitution appears to be partly responsible for the increased inhibitory activity of viperistatin over obtustatin.",

keywords = "BSA, bovine serum albumin, CMFDA, 5-chloromethylfluorescein diacetate, HPLC, high-performance liquid chromatography, MALDI-TOF, matrix-assisted laser-desorption ionization time-of-flight mass spectrometry, TFA, trifluoroacetic acid",

author = "Kisiel, {Dariusz G.} and Calvete, {Juan J.} and Jehoshua Katzhendler and Andrzej Fertala and Philip Lazarovici and Cezary Marcinkiewicz",

year = "2004",

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day = "19",

doi = "10.1016/j.febslet.2004.10.050",

language = "אנגלית",

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T1 - Structural determinants of the selectivity of KTS-disintegrins for the α1β1 integrin

AU - Kisiel, Dariusz G.

AU - Calvete, Juan J.

AU - Katzhendler, Jehoshua

AU - Fertala, Andrzej

AU - Lazarovici, Philip

AU - Marcinkiewicz, Cezary

PY - 2004/11/19

Y1 - 2004/11/19

N2 - KTS-disintegrins are a subfamily of short monomeric disintegrins that are potent and selective inhibitors of α1β1 integrin. The amino acid sequence of the new KTS-disintegrin, viperistatin, differs from previously characterized obtustatin in three residues at position 24 (within the integrin binding loop), 38 (hydrophobic core) and 40 (C-terminal region). Noteworthy, viperistatin is about 25-fold more potent than obtustatin inhibiting the binding of this integrin to collagen IV. Synthetic peptides representing the full-length of integrin-binding loops of these disintegrins showed that the Leu24/Arg substitution appears to be partly responsible for the increased inhibitory activity of viperistatin over obtustatin.

AB - KTS-disintegrins are a subfamily of short monomeric disintegrins that are potent and selective inhibitors of α1β1 integrin. The amino acid sequence of the new KTS-disintegrin, viperistatin, differs from previously characterized obtustatin in three residues at position 24 (within the integrin binding loop), 38 (hydrophobic core) and 40 (C-terminal region). Noteworthy, viperistatin is about 25-fold more potent than obtustatin inhibiting the binding of this integrin to collagen IV. Synthetic peptides representing the full-length of integrin-binding loops of these disintegrins showed that the Leu24/Arg substitution appears to be partly responsible for the increased inhibitory activity of viperistatin over obtustatin.

KW - BSA, bovine serum albumin

KW - CMFDA, 5-chloromethylfluorescein diacetate

KW - HPLC, high-performance liquid chromatography

KW - MALDI-TOF, matrix-assisted laser-desorption ionization time-of-flight mass spectrometry

KW - TFA, trifluoroacetic acid

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AN - SCOPUS:8844224111

SN - 0014-5793

VL - 577

SP - 478

EP - 482

JO - FEBS Letters

JF - FEBS Letters

IS - 3

ER -

Structural determinants of the selectivity of KTS-disintegrins for the α1β1 integrin

Abstract

Keywords

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