TY - JOUR
T1 - Rational improvement of the affinity and selectivity of integrin binding of grafted lasso peptides
AU - Hegemann, Julian D.
AU - De Simone, Mariarosaria
AU - Zimmermann, Marcel
AU - Knappe, Thomas A.
AU - Xie, Xiulan
AU - Di Leva, Francesco Saverio
AU - Marinelli, Luciana
AU - Novellino, Ettore
AU - Zahler, Stefan
AU - Kessler, Horst
AU - Marahiel, Mohamed A.
PY - 2014/7/10
Y1 - 2014/7/10
N2 - Integrins moderate diverse important functions in the human body and are promising targets in cancer therapy. Hence, the selective inhibition of specific integrins is of great medicinal interest. Here, we report the optimization of a grafted lasso peptide, yielding MccJ25(RGDF), which is a highly potent and selective αvβ3 integrin inhibitor. Furthermore, its NMR structure was elucidated and employed in a molecular dynamics approach, revealing information about the integrin binding mode and selectivity profile of MccJ25(RGDF).
AB - Integrins moderate diverse important functions in the human body and are promising targets in cancer therapy. Hence, the selective inhibition of specific integrins is of great medicinal interest. Here, we report the optimization of a grafted lasso peptide, yielding MccJ25(RGDF), which is a highly potent and selective αvβ3 integrin inhibitor. Furthermore, its NMR structure was elucidated and employed in a molecular dynamics approach, revealing information about the integrin binding mode and selectivity profile of MccJ25(RGDF).
UR - http://www.scopus.com/inward/record.url?scp=84904336652&partnerID=8YFLogxK
U2 - 10.1021/jm5004478
DO - 10.1021/jm5004478
M3 - Article
C2 - 24949551
AN - SCOPUS:84904336652
SN - 0022-2623
VL - 57
SP - 5829
EP - 5834
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 13
ER -
