Reversed binding of a small molecule ligand in homologous chemokine receptors - differential role of extracellular loop 2.

ABSTRACT:

Background and purpose

The majority of small molecule compounds targeting chemokine receptors share a similar pharmacophore with a centrally located aliphatic positive charge and flanking aromatic moieties. Here we describe a novel piperidine-based compound with structural similarity to previously described CCR8-specific agonists, but containing a unique phenyl-tetrazol moiety which, in addition to activity at CCR8 was also active at CCR1.

Experimental approach

Single point mutations were introduced in CCR1 and CCR8, and their effect on small molecule ligand-induced receptor activation was examined through inositol trisphosphate (IP(3) ) accumulation. The molecular interaction profile of the agonist was verified by molecular modeling.

Key results

The chemokine recepto

SUBMITTER: Jensen PC 

PROVIDER: S-EPMC3415653 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature