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-potent02336nas a2200349   4500008004100000022001400041245008500055210006900140260000900209300001400218490000700232520122800239100002201467700002201489700002101511700002701532700002501559700002601584700002001610700002201630700001901652700002601671700001901697700002301716700003201739700002301771700002201794700001701816700002201833700001901855856011201874       2019                        eng d  a0022-262300aSelective targeting of integrin alpha v beta 8 by a highly active cyclic peptide0 aSelective targeting of integrin alpha v beta 8 by a highly activ  cFEB   a2024-20370 v623 a<p>Integrins play important roles in physiological and pathophysiological processes. Among the RGD-recognizing integrin subtypes, the alpha v beta 8 receptor is emerging as an attractive target because of its involvement in various illnesses, such as autoimmune diseases, viral infections, and cancer. However, its functions have, so far, not been investigated in living subjects mainly because of the lack of a selective alpha v beta 8 ligand. Here, we report the design and potential medical applications of a cyclic octapeptide as the first highly selective small-molecule ligand for alpha v beta 8. Remarkably, this compound displays low nanomolar alpha v beta 8 binding affinity and a strong discriminating power of at least 2 orders of magnitude versus other RGD-recognizing integrins. Peptide functionalization with fluorescent or radioactive labels enables the selective imaging of alpha v beta 8-positive cells and tissues. This new probe will pave the way for detailed characterization of the distinct (patho)physiological role of this relatively unexplored integrin, providing a basis to fully exploit the potential of alpha v beta 8 as a target for molecular diagnostics and personalized therapy regimens.</p>
1 aReichart, Florian1 aMaltsev, Oleg, V.1 aKapp, Tobias, G.1 aRaeder, Andreas, F. B.1 aWeinmueller, Michael1 aMarelli, Udaya, Kiran1 aNotni, Johannes1 aWurzer, Alexander1 aBeck, Roswitha1 aWester, Hans, Juergen1 aSteiger, Katja1 aDi Maro, Salvatore1 aDi Leva, Francesco, Saverio1 aMarinelli, Luciana1 aNieberler, Markus1 aReuning, Ute1 aSchwaiger, Markus1 aKessler, Horst  uhttps://library.ncl.res.in/content/selective-targeting-integrin-alpha-v-beta-8-highly-active-cyclic-peptide