Premium
Design and pharmacological characterization of VUF14480 , a covalent partial agonist that interacts with cysteine 98 3.36 of the human histamine H 4 receptor
Author(s) -
Nijmeijer S,
Engelhardt H,
Schultes S,
Stolpe A C,
Lusink V,
Graaf C,
Wijtmans M,
Haaksma E E J,
Esch I J P,
Stachurski K,
Vischer H F,
Leurs R
Publication year - 2013
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12113
Subject(s) - covalent bond , cysteine , chemistry , receptor , g protein coupled receptor , stereochemistry , agonist , serine , histamine receptor , residue (chemistry) , biochemistry , enzyme , antagonist , organic chemistry
The recently proposed binding mode of 2-aminopyrimidines to the human (h) histamine H₄ receptor suggests that the 2-amino group of these ligands interacts with glutamic acid residue E182(5.46) in the transmembrane (TM) helix 5 of this receptor. Interestingly, substituents at the 2-position of this pyrimidine are also in close proximity to the cysteine residue C98(3.36) in TM3. We hypothesized that an ethenyl group at this position will form a covalent bond with C98(3.36) by functioning as a Michael acceptor. A covalent pyrimidine analogue will not only prove this proposed binding mode, but will also provide a valuable tool for H4 receptor research.