Novel Macrocyclic Antagonists of the CGRP Receptor Part 2: Stereochemical Inversion Induces an Unprecedented Binding Mode (CROSBI ID 323833)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
Southall, Stacey, M. ; Banerjee, Joydeep ; Brown, Jason ; Butkovic, Kristina ; Cansfield, Andrew D. ; Cansfield, Julie, E. ; Congreve, Miles S. ; Cseke, Gabriella ; Deflorian, Franceska ; Petrovic Hunjadi, Martina ; Hutinec, Antun ; Kumar Inturi, Trinadh ; Rupcic, Renata ; Saxty, Gordon ; Watson, Stephen P.
engleski
Novel Macrocyclic Antagonists of the CGRP Receptor Part 2: Stereochemical Inversion Induces an Unprecedented Binding Mode
The diastereomeric macrocyclic calcitonin generelated peptide (CGRP) antagonists HTL0029881 (3) and HTL0029882 (4), in which the stereochemistry of a spiro center is reversed, surprisingly demonstrate comparable potency. X-ray crystallographic characterization demonstrates that 3 binds to the CGRP receptor in a precedented manner but that 4 binds in an unprecedented, unexpected, and radically different manner. The observation of this phenomenon is noteworthy and may open novel avenues for CGRP receptor antagonist design.
GPCR, CGRP, CGRPR, Macrocycle, Macrocyclic, Antagonist
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Podaci o izdanju
13 (11)
2022.
1776-1782
objavljeno
1948-5875
10.1021/acsmedchemlett.2c00400
