From a helix to a small cycle: metadynamics-inspired alpha v beta 6 integrin selective ligands
| Title | From a helix to a small cycle: metadynamics-inspired alpha v beta 6 integrin selective ligands |
| Publication Type | Journal Article |
| Year of Publication | 2018 |
| Authors | Di Leva, FSaverio, Tomassi, S, Di Maro, S, Reichart, F, Notni, J, Dangi, A, Marelli, UKiran, Brancaccio, D, Merlino, F, Wester, H-J, Novellino, E, Kessler, H, Marinelli, L |
| Journal | Angewandte Chemie-International Edition |
| Volume | 57 |
| Issue | 44 |
| Pagination | 14645-14649 |
| Date Published | OCT |
| Type of Article | Article |
| ISSN | 1433-7851 |
| Abstract | The 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. |
| DOI | 10.1002/anie.201803250 |
| Type of Journal (Indian or Foreign) | Foreign |
| Impact Factor (IF) | 12.102 |
Divison category:
Organic Chemistry
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