In Search of the Optimal Macrocyclization Site for Neurotensin
American Chemical Society, 2018
academicJournal
Zugriff:
[Image: see text] Neurotensin exerts potent analgesic effects following activation of its cognate GPCRs. In this study, we describe a systematic exploration, using structure-based design, of conformationally constraining neurotensin (8–13) with the help of macrocyclization and the resulting impacts on binding affinity, signaling, and proteolytic stability. This exploratory study led to a macrocyclic scaffold with submicromolar binding affinity, agonist activity, and greatly improved plasma stability.
Titel: |
In Search of the Optimal Macrocyclization Site for Neurotensin
|
---|---|
Autor/in / Beteiligte Person: | Sousbie, Marc ; Besserer-Offroy, Élie ; Brouillette, Rebecca L. ; Longpré, Jean-Michel ; Leduc, Richard ; Sarret, Philippe ; Marsault, Éric |
Link: | |
Veröffentlichung: | American Chemical Society, 2018 |
Medientyp: | academicJournal |
DOI: | 10.1021/acsmedchemlett.7b00500 |
Sonstiges: |
|