Application of fragment growing and fragment linking to the discovery of inhibitors of Mycobacterium tuberculosis pantothenate synthetase

TY - JOUR

T1 - Application of fragment growing and fragment linking to the discovery of inhibitors of Mycobacterium tuberculosis pantothenate synthetase

AU - Hung, A.W.

AU - Silvestre, H.L.

AU - Wen, S.

AU - Ciulli, Alessio

AU - Blundell, T.L.

AU - Abell, C.

N1 - MEDLINE® is the source for the MeSH terms of this document.

PY - 2009/10/26

Y1 - 2009/10/26

N2 - Two distinct strategies uncovered potent inhibitors of the title enzyme. X-ray crystallography and isothermal titration calorimetry guided the systematic elaboration of fragments identified from biophysical screens. The excellent inhibitor shown in the enzyme active site on the right was formed by connection of the lead fragments (left) with an acyl sulfonamide linker and resembles the best inhibitor discovered by the fragment-growing strategy.

AB - Two distinct strategies uncovered potent inhibitors of the title enzyme. X-ray crystallography and isothermal titration calorimetry guided the systematic elaboration of fragments identified from biophysical screens. The excellent inhibitor shown in the enzyme active site on the right was formed by connection of the lead fragments (left) with an acyl sulfonamide linker and resembles the best inhibitor discovered by the fragment-growing strategy.

UR - https://www.scopus.com/pages/publications/70350346470

U2 - 10.1002/anie.200903821

DO - 10.1002/anie.200903821

M3 - Article

AN - SCOPUS:70350346470

SN - 1433-7851

VL - 48

SP - 8452

EP - 8456

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 45

ER -