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Inside Back Cover: Fragment Deconstruction of Small, Potent Factor Xa Inhibitors: Exploring the Superadditivity Energetics of Fragment Linking in Protein–Ligand Complexes (Angew. Chem. Int. Ed. 4/2012)
Author(s) -
Nazaré Marc,
Matter Hans,
Will David W.,
Wagner Michael,
Urmann Matthias,
Czech Jörg,
Schreuder Herman,
Bauer Armin,
Ritter Kurt,
Wehner Volkmar
Publication year - 2012
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201108620
Subject(s) - superadditivity , fragment (logic) , affinities , stereochemistry , energetics , chemistry , deconstruction (building) , ligand (biochemistry) , linker , receptor , physics , biology , biochemistry , mathematics , computer science , ecology , mathematical economics , algorithm , operating system , thermodynamics
The superadditivity of fragment linking on affinities was quantified by systematic deconstruction of a fXa inhibitor. In their Communication on page 905 ff., M. Nazaré, H. Matter, and co‐workers show that by connecting two fragments with a single bond, a linker contribution of −14.0 kJ mol −1 results, which corresponds to an affinity improvement of about 2.5 orders of magnitude relative to the sum of fragment affinities.