Towards synthetic adrenaline receptors--shape-selective adrenaline recognition in water.
In spite of their key role in signal transduction, the mechanism of action of adrenergic receptors is still poorly understood. We have imitated the postulated binding pattern of the large membrane protein with a small, rationally designed synthetic host molecule. Experimental evidence is presented for the simultaneous operation of electrostatic attraction, hydrogen bonds, pi stacking, and hydrophobic interactions. By virtue of this combination of weak attractive forces, adrenaline derivatives in water are bound with high shape selectivity for the slim dopamine skeleton. We think that these findings support the postulated cooperative interplay of noncovalent interactions in the natural receptors. In addition, they provide access to a new type of adrenaline sensor. This may be the first step towards an artificial signal-transduction system.
Herm
Michael
M
Dupont, Wuppertal, Germany.
Molt
Oliver
O
Schrader
Thomas
T
D001665:Binding Sites; D015306:Biogenic Monoamines / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D063065:Organophosphonates / Q000737:chemistry; D011485:Protein Binding; D011941:Receptors, Adrenergic / Q000737:chemistry* / Q000378:metabolism; D012996:Solutions; D013379:Substrate Specificity; D014867:Water
D015306:Biogenic Monoamines; D063065:Organophosphonates; D011941:Receptors, Adrenergic; D012996:Solutions; D014867:Water; D004837:Epinephrine