Design and pharmacological characterization of  VUF14480 , a covalent partial agonist that interacts with cysteine 98 3.36  of the human histamine  H 4   receptor | Zendy

Nijmeijer S | Zendy; Engelhardt H | Zendy; Schultes S | Zendy; Stolpe A C | Zendy; Lusink V | Zendy; Graaf C | Zendy; Wijtmans M | Zendy; Haaksma E E J | Zendy; Esch I J P | Zendy; Stachurski K | Zendy; Vischer H F | Zendy; Leurs R | Zendy

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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.

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