01692nas a2200289   4500008004100000022001500041245009900056210006900155260000800224300001600232490000700248520073200255100003200987700002101019700002301040700002201063700002001085700001601105700002601121700002201147700002301169700002501192700002201217700001901239700002301258856012101281       2018                        eng d  a 1433-785100aFrom a helix to a small cycle: metadynamics-inspired alpha v beta 6 integrin selective ligands0 aFrom a helix to a small cycle metadynamicsinspired alpha v beta   cOCT  a14645-146490 v573 aThe RGD-recognizing alpha v beta 6 integrin has only recently emerged as a major target for cancer diagnosis and therapy. Thus, the development of selective, low-molecular-weight ligands of this receptor is still in great demand. Here, a metadynamics-driven design strategy allowed us to successfully convert a helical nonapeptide into a cyclic pentapeptide (6) showing remarkable potency and alpha v beta 6 specificity. NMR and docking studies elucidated the reasons for the high affinity and selectivity of this compound, setting the ground for the rational design of new alpha v beta 6-specific small peptides or even peptidomimetics. In vivo PET imaging studies demonstrated the potential use of 6 for medical applications.1 aDi Leva, Francesco, Saverio1 aTomassi, Stefano1 aDi Maro, Salvatore1 aReichart, Florian1 aNotni, Johannes1 aDangi, Abha1 aMarelli, Udaya, Kiran1 aBrancaccio, Diego1 aMerlino, Francesco1 aWester, Hans-Juergen1 aNovellino, Ettore1 aKessler, Horst1 aMarinelli, Luciana  uhttps://library.ncl.res.in/content/helix-small-cycle-metadynamics-inspired-alpha-v-beta-6-integrin-selective-ligands01727nas a2200301   4500008004100000022001400041245012600055210006900181260000800250300001400258490000700272520069800279100002100977700003200998700002001030700002701050700002401077700002201101700001901123700002201142700001901164700002201183700002601205700002501231700002301256700001901279856012701298       2018                        eng d  a0022-262300aN-Methylation of isoDGR peptides: discovery of a selective alpha 5 beta 1-integrin ligand as a potent tumor imaging agent0 aNMethylation of isoDGR peptides discovery of a selective alpha 5  cMAR  a2490-24990 v613 a<p>Specific targeting of the integrin subtype alpha 5 beta 1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective alpha 5 beta 1/alpha v beta 6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding aSfil 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 alpha 5 beta 1 integrin expression in a M21 mouse xenograft.</p>1 aKapp, Tobias, G.1 aDi Leva, Francesco, Saverio1 aNotni, Johannes1 aRaeder, Andreas, F. B.1 aFottner, Maximilian1 aReichart, Florian1 aReich, Dominik1 aWurzer, Alexander1 aSteiger, Katja1 aNovellino, Ettore1 aMarelli, Udaya, Kiran1 aWester, Hans-Juergen1 aMarinelli, Luciana1 aKessler, Horst  uhttps://library.ncl.res.in/content/n-methylation-isodgr-peptides-discovery-selective-alpha-5-beta-1-integrin-ligand-potent