Polyethylene glycol-based homologated ligands for nicotinic acetylcholine receptors

A homologous series of polyethylene glycol (PEG) monomethyl ethers were conjugated with three ligand series for nicotinic acetylcholine receptors. Conjugates of acetylaminocholine, the cyclic analog 1-acetyl-4,4-dimethylpiperazinium, and pyridyl ether A-84543 were prepared. Each series was found to retain significant affinity at nicotinic receptors in rat cerebral cortex with tethers of up to six PEG units. Such compounds are hydrophilic ligands which may serve as models for fluorescent/affinity probes and multivalent ligands for nAChR.

Three series of homologated ligands were synthesized and assessed for nicotinic receptor binding in rat cerebral cortex. Each series displayed affinity at nicotinic receptors that decreased slowly with increasing chain length.Figure optionsDownload as PowerPoint slide