N -Methylation of iso DGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent

Tobias G. Kapp; Francesco Saverio Di Leva; Johannes Notni; Andreas F.B. Räder; Maximilian Fottner; Florian Reichart; Dominik Reich; Alexander Wurzer; Katja Steiger; Ettore Novellino; Udaya Kiran Marelli; Hans Jürgen Wester; Luciana Marinelli; Horst Kessler

doi:10.1021/acs.jmedchem.7b01752

N -Methylation of iso DGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent

Tobias G. Kapp
, Francesco Saverio Di Leva
, Johannes Notni
, Andreas F.B. Räder
, Maximilian Fottner
, Florian Reichart
, Dominik Reich
, Alexander Wurzer
, Katja Steiger
, Ettore Novellino
, Udaya Kiran Marelli
, Hans Jürgen Wester
, Luciana Marinelli
, Horst Kessler

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

20 Scopus citations

Abstract

Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg-isoDGR-(NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg-isoDGR-(NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.

Original language	English
Pages (from-to)	2490-2499
Number of pages	10
Journal	Journal of Medicinal Chemistry
Volume	61
Issue number	6
DOIs	https://doi.org/10.1021/acs.jmedchem.7b01752
State	Published - 22 Mar 2018

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Kapp, T. G., Di Leva, F. S., Notni, J., Räder, A. F. B., Fottner, M., Reichart, F., Reich, D., Wurzer, A., Steiger, K., Novellino, E., Marelli, U. K., Wester, H. J., Marinelli, L., & Kessler, H. (2018). N -Methylation of iso DGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent. Journal of Medicinal Chemistry, 61(6), 2490-2499. https://doi.org/10.1021/acs.jmedchem.7b01752

@article{99b34089b146477fb7acd56927f9aeaa,

title = "N -Methylation of iso DGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent",

abstract = "Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg-isoDGR-(NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg-isoDGR-(NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.",

author = "Kapp, \{Tobias G.\} and \{Di Leva\}, \{Francesco Saverio\} and Johannes Notni and R{\"a}der, \{Andreas F.B.\} and Maximilian Fottner and Florian Reichart and Dominik Reich and Alexander Wurzer and Katja Steiger and Ettore Novellino and Marelli, \{Udaya Kiran\} and Wester, \{Hans J{\"u}rgen\} and Luciana Marinelli and Horst Kessler",

note = "Publisher Copyright: {\textcopyright} 2018 American Chemical Society.",

year = "2018",

month = mar,

day = "22",

doi = "10.1021/acs.jmedchem.7b01752",

language = "English",

volume = "61",

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Kapp, TG, Di Leva, FS, Notni, J, Räder, AFB, Fottner, M, Reichart, F, Reich, D, Wurzer, A, Steiger, K, Novellino, E, Marelli, UK, Wester, HJ, Marinelli, L & Kessler, H 2018, 'N -Methylation of iso DGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent', Journal of Medicinal Chemistry, vol. 61, no. 6, pp. 2490-2499. https://doi.org/10.1021/acs.jmedchem.7b01752

TY - JOUR

T1 - N -Methylation of iso DGR Peptides

T2 - Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent

AU - Kapp, Tobias G.

AU - Di Leva, Francesco Saverio

AU - Notni, Johannes

AU - Räder, Andreas F.B.

AU - Fottner, Maximilian

AU - Reichart, Florian

AU - Reich, Dominik

AU - Wurzer, Alexander

AU - Steiger, Katja

AU - Novellino, Ettore

AU - Marelli, Udaya Kiran

AU - Wester, Hans Jürgen

AU - Marinelli, Luciana

AU - Kessler, Horst

PY - 2018/3/22

Y1 - 2018/3/22

N2 - Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg-isoDGR-(NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg-isoDGR-(NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.

AB - Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg-isoDGR-(NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling clarified the molecular basis of its improved selectivity profile. To demonstrate its potential in vivo, c(phg-isoDGR-(NMe)k) was trimerized with the chelator TRAP and used as a positron-emission tomography tracer for monitoring α5β1 integrin expression in a M21 mouse xenograft.

UR - https://www.scopus.com/pages/publications/85044230813

U2 - 10.1021/acs.jmedchem.7b01752

DO - 10.1021/acs.jmedchem.7b01752

M3 - Article

C2 - 29489355

AN - SCOPUS:85044230813

SN - 0022-2623

VL - 61

SP - 2490

EP - 2499

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 6

ER -

N -Methylation of iso DGR Peptides: Discovery of a Selective α5β1-Integrin Ligand as a Potent Tumor Imaging Agent

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