Premium
Screening of a Novel Fragment Library with Functional Complexity against Mycobacterium tuberculosis InhA
Author(s) -
Prati Federica,
Zuccotto Fabio,
Fletcher Daniel,
Convery Maire A.,
FernandezMenendez Raquel,
Bates Robert,
Encinas Lourdes,
Zeng Jingkun,
Chung Chunwa,
De Dios Anton Paco,
MendozaLosana Alfonso,
Mackenzie Claire,
Green Simon R.,
Huggett Margaret,
Barros David,
Wyatt Paul G.,
Ray Peter C.
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700774
Subject(s) - inha , mycobacterium tuberculosis , fragment (logic) , tuberculosis , elaboration , ligand efficiency , computational biology , biology , ligand (biochemistry) , combinatorial chemistry , chemistry , biochemistry , medicine , computer science , receptor , programming language , philosophy , pathology , humanities
Our findings reported herein provide support for the benefits of including functional group complexity (FGC) within fragments when screening against protein targets such as Mycobacterium tuberculosis InhA. We show that InhA fragment actives with FGC maintained their binding pose during elaboration. Furthermore, weak fragment hits with functional group handles also allowed for facile fragment elaboration to afford novel and potent InhA inhibitors with good ligand efficiency metrics for optimization.