32622-40-5Relevant articles and documents
Structure-Based Identification of Novel Ligands Targeting Multiple Sites within a Chemokine-G-Protein-Coupled-Receptor Interface
Smith, Emmanuel W.,Nevins, Amanda M.,Qiao, Zhen,Liu, Yan,Getschman, Anthony E.,Vankayala, Sai L.,Kemp, M. Trent,Peterson, Francis C.,Li, Rongshi,Volkman, Brian F.,Chen, Yu
, p. 4342 - 4351 (2016)
CXCL12 is a human chemokine that recognizes the CXCR4 receptor and is involved in immune responses and metastatic cancer. Interactions between CXCL12 and CXCR4 are an important drug target but, like other elongated protein-protein interfaces, present challenges for small molecule ligand discovery due to the relatively shallow and featureless binding surfaces. Calculations using an NMR complex structure revealed a binding hot spot on CXCL12 that normally interacts with the I4/I6 residues from CXCR4. Virtual screening was performed against the NMR model, and subsequent testing has verified the specific binding of multiple docking hits to this site. Together with our previous results targeting two other binding pockets that recognize sulfotyrosine residues (sY12 and sY21) of CXCR4, including a new analog against the sY12 binding site reported herein, we demonstrate that protein-protein interfaces can often possess multiple sites for engineering specific small molecule ligands that provide lead compounds for subsequent optimization by fragment based approaches.
The synthesis of novel 2,4,6-trisubstituted 1,3,5-triazines: A search for potential murf enzyme inhibitors
Sosic, Izidor,Stefane, Bogdan,Kovac, Andreja,Turk, Samo,Blanot, Didier,Gobec, Stanislav
experimental part, p. 91 - 115 (2010/05/19)
A series of new 2,4,6-trisubstituted 1,3,5-triazines, possessing a variety of substituents (-OH, -SH, -OMe, -Cl, -HNR, -SR and amino acid moieties), were synthesized and evaluated for the inhibition of the bacterial peptidoglycan biosynthesis enzyme MurF.
