Conformational Control of Integrin-Subtype Selectivity in isoDGR Peptide Motifs: A Biological Switch

被引：63

作者：

Frank, Andreas O. ^{[1
]}

Otto, Elke ^{[1
]}

Mas-Moruno, Carlos ^{[1
]}

Schiller, Herbert B. ^{[3
]}

Marinelli, Luciana ^{[2
]}

Cosconati, Sandro ^{[2
]}

Bochen, Alexander ^{[1
]}

Vossmeyer, Doerte ^{[4
]}

Zahn, Grit ^{[4
]}

Stragies, Roland ^{[4
]}

Novellino, Ettore ^{[2
]}

Kessler, Horst ^{[1
]}

机构：

[1] Tech Univ Munich, Dept Chem, Inst Adv Study, D-85747 Garching, Germany

[2] Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicolog, I-80131 Naples, Italy

[3] Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany

[4] Jerini AG, D-10115 Berlin, Germany

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2010年 / 49卷 / 48期

关键词：

cyclic pentapeptides; integrin ligands; isoDGR sequence; NMR spectroscopy; peptides; CYCLIC PENTAPEPTIDES; FIBRONECTIN; RESIDUES; LIGANDS; BINDING; ALPHA(5)BETA(1); ALPHA-V-BETA-3; DEAMIDATION; SEQUENCES; DESIGN;

D O I：

10.1002/anie.201004363

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The rearrangement of asparagine to isoaspartate (isoD) is responsible for the deactivation of many functional proteins. However, the isoDGR motif, which is optimally presented as a conformationally controlled cyclic pentapeptide, binds selectively to α5β 1 integrin (see the docking model) with an affinity comparable to that of the peptidic antitumor agent Cilengitide. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：9278 / 9281

页数：4

共 30 条

[1] ARG-GLY-ASP CONSTRAINED WITHIN CYCLIC PENTAPEPTIDES - STRONG AND SELECTIVE INHIBITORS OF CELL-ADHESION TO VITRONECTIN AND LAMININ FRAGMENT-P1 [J].

AUMAILLEY, M ;

GURRATH, M ;

MULLER, G ;

CALVETE, J ;

TIMPL, R ;

KESSLER, H .

FEBS LETTERS, 1991, 291 (01) :50-54

[2]

BODANZSKY M, 1993, PRINCIPLES PEPTIDE S, P202

[3] The neovasculature homing motif NGR: more than meets the eye [J].

Corti, Angelo ;

Curnis, Flavio ;

Arap, Wadih ;

Pasqualini, Renata .

BLOOD, 2008, 112 (07) :2628-2635

[4] Spontaneous formation of L-isoaspartate and gain of function in fibronectin [J].

Curnis, Flavio ;

Longhi, Renato ;

Crippa, Luca ;

Cattaneo, Angela ;

Dondossola, Eleonora ;

Bachi, Angela ;

Corti, Angelo .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (47) :36466-36476

[5] Critical Role of Flanking Residues in NGR-to-isoDGR Transition and CD13/Integrin Receptor Switching [J].

Curnis, Flavio ;

Cattaneo, Angela ;

Longhi, Renato ;

Sacchi, Angelina ;

Gasparri, Anna Maria ;

Pastorino, Fabio ;

Di Matteo, Paola ;

Traversari, Catia ;

Bachi, Angela ;

Ponzoni, Mirco ;

Rizzardi, Gian-Paolo ;

Corti, Angelo .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (12) :9114-9123

[6] N-methylated cyclic RGD peptides as highly active and selective αvβ3 integrin antagonists [J].

Dechantsreiter, MA ;

Planker, E ;

Mathä, B ;

Lohof, E ;

Hölzemann, G ;

Jonczyk, A ;

Goodman, SL ;

Kessler, H .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (16) :3033-3040

[7] Immunogenic and structural properties of the Asn-Gly-Arg (NGR) tumor neovasculature-homing motif [J].

Di Matteo, P ;

Curnis, F ;

Longhi, R ;

Colombo, G ;

Sacchi, A ;

Crippa, L ;

Protti, MP ;

Ponzoni, M ;

Toma, S ;

Corti, A .

MOLECULAR IMMUNOLOGY, 2006, 43 (10) :1509-1518

[8] The Role of Protein L-Isoaspartyl/D-Aspartyl O-Methyltransferase (PIMT) in Intracellular Signal Transduction [J].

Furuchi, Takemitsu ;

Sakurako, Kosugi ;

Katane, Masumi ;

Sekine, Masae ;

Homma, Hiroshi .

CHEMISTRY & BIODIVERSITY, 2010, 7 (06) :1337-1348

[9]

GEIGER T, 1987, J BIOL CHEM, V262, P785

[10] Structural and functional aspects of RGD-containing cyclic pentapeptides as highly potent and selective integrin alpha(v)beta(3) antagonists [J].

Haubner, R ;

Gratias, R ;

Diefenbach, B ;

Goodman, SL ;

Jonczyk, A ;

Kessler, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (32) :7461-7472

← 1 2 3 →