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.

[1]  T. Schrader,et al.  Auf dem Weg zu synthetischen Adrenalinrezeptoren – formselektive Adrenalin‐Erkennung in Wasser , 2001 .

[2]  T. Schrader,et al.  Towards Synthetic Adrenaline Receptors-Shape-Selective Adrenaline Recognition in Water. , 2001, Angewandte Chemie.

[3]  S. Liggett.  Pharmacogenetics of Beta-1- and Beta-2-Adrenergic Receptors , 2000, Pharmacology.

[4]  K. Palczewski,et al.  Crystal Structure of Rhodopsin: A G‐Protein‐Coupled Receptor , 2002, Chembiochem : a European journal of chemical biology.

[5]  G. Tocchini-Valentini,et al.  Molecular recognition of amino acids by RNA aptamers: the evolution into an L-tyrosine binder of a dopamine-binding RNA motif. , 2000, RNA.

[6]  M. Bristow.  β-Adrenergic Receptor Blockade in Chronic Heart Failure , 2000 .

[7]  Thomas Schrader,et al.  Towards synthetic adrenaline receptors. , 2000, Chemistry.

[8]  A. Himmelmann.  New Information on the Role of Beta-Blockers in Cardiac Therapy , 1999, Cardiovascular Drugs and Therapy.

[9]  Y. Umezawa,et al.  Dopamine-selective response in membrane potential by homooxacalix[3]arene triether host incorporated in PVC liquid membrane. , 1999, Bioorganic & medicinal chemistry letters.

[10]  Ana Martínez,et al.  SELECTIVE DOPAMINE RECEPTORS : SYNTHESIS, COMPLEXING PROPERTIES, AND MOLECULAR MODELLING STUDIES OF NEW PODANDS DERIVED FROM 4-HYDROXY-1H-PYRAZOLE , 1999 .

[11]  F. Diederich,et al.  Modeling the Supramolecular Properties of Aliphatic-Aromatic Hydrocarbons with Convex-Concave Topology. , 1998, Angewandte Chemie.

[12]  T. Mallouk,et al.  Chiral Molecular Recognition in a Tripeptide Benzylviologen Cyclophane Host , 1998 .

[13]  A. P. Davis,et al.  A Tricyclic Polyamide Receptor for Carbohydrates in Organic Media. , 1998, Angewandte Chemie.

[14]  Anthony P. Davis,et al.  Ein tricyclisches Polyamid als Rezeptor für Kohlenhydrate in organischen Medien , 1998 .

[15]  M. Collinson,et al.  Template Recognition in Inorganic−Organic Hybrid Films Prepared by the Sol−Gel Process , 1998 .

[16]  K. Nakanishi,et al.  Zinc Porphyrin Tweezer in Host−Guest Complexation: Determination of Absolute Configurations of Diamines, Amino Acids, and Amino Alcohols by Circular Dichroism , 1998 .

[17]  George M. Whitesides,et al.  Estimating the Entropic Cost of Self-Assembly of Multiparticle Hydrogen-Bonded Aggregates Based on the Cyanuric Acid·Melamine Lattice , 1998 .

[18]  D. A. Jeyaraj,et al.  An Investigation of the Diastereoselectivity of Nucleophilic Additions to 6-Methyl-1-oxa-4-thiaspiro[4.5]dec-6-ene-7-carbaldehyde. Hybridization of the Nucleophile Alters the Diastereoselectivity† , 1998 .

[19]  Jong‐In Hong,et al.  Efficient dopamine transport by a crown phosphonate , 1998 .

[20]  B. Chait,et al.  The structure of the potassium channel: molecular basis of K+ conduction and selectivity. , 1998, Science.

[21]  Hongyuan Chen,et al.  The Molecular Recognition Characteristics of ω-Mercapto Methoxy Poly(Ethylene Glycol) Self-Assembled Monolayers at a Gold Electrode and Its Application for Detection of Dopamine in Serum , 1998 .

[22]  Thomas Schrader,et al.  TOWARD SYNTHETIC ADRENALINE RECEPTORS : STRONG, SELECTIVE, AND BIOMIMETIC RECOGNITION OF BIOLOGICALLY ACTIVE AMINO ALCOHOLS BY BISPHOSPHONATE RECEPTOR MOLECULES , 1998 .

[23]  E. Pebay-Peyroula,et al.  X-ray structure of bacteriorhodopsin at 2.5 angstroms from microcrystals grown in lipidic cubic phases. , 1997, Science.

[24]  H. Krawczyk.  A Convenient Route for Monodealkylation of Diethyl Phosphonates , 1997 .

[25]  D. A. Dougherty,et al.  The Cationminus signpi Interaction. , 1997, Chemical reviews.

[26]  R. Vivilecchia,et al.  Chiral separation of primary amino compounds using a non-chiral crown ether with beta-cyclodextrin by capillary electrophoresis. , 1997, Journal of chromatography. B, Biomedical sciences and applications.

[27]  A. Samat,et al.  A Proton-Ionizable Ester Crown of 3,5-Disubstituted 1H-Pyrazole Able To Form Stable Dinuclear Complexes with Lipophilic Phenethylamines. , 1997, The Journal of organic chemistry.

[28]  T. Schrader.  AUF DEM WEG ZU SYNTHETISCHEN ADRENALINREZEPTOREN : STARKE BINDUNG VON AMINOALKOHOLEN DURCH BISPHOSPHONATE , 1996 .

[29]  Bradley D. Smith,et al.  FACILITATED CATECHOLAMINE TRANSPORT THROUGH BULK AND POLYMER-SUPPORTED LIQUID MEMBRANES , 1996 .

[30]  F. Diederich,et al.  A New Family of Chiral Binaphthyl‐Derived Cyclophane Receptors: Complexation of Pyranosides , 1995 .

[31]  S. Anderson,et al.  Eine neue Klasse chiraler, von 1,1′‐Binaphthyl abgeleiteter Cyclophan‐Rezeptoren: Komplexierung von Pyranosiden , 1995 .

[32]  J. Lehn,et al.  Binding of acetylcholine and other quaternary ammonium cations by sulfonated calixarenes. Crystal structure of a [choline-tetrasulfonated calix[4]arene] complex , 1995 .

[33]  Bradley D. Smith,et al.  Selective Dopamine Transport Using a Crown Boronic Acid , 1994 .

[34]  T. Ishizu,et al.  Complex formation of cyclo(L-Phe-L-Pro)4 with noradrenaline hydrochloride. , 1994, Chemical and pharmaceutical bulletin.

[35]  F. Erni,et al.  Enantiomeric separations in capillary zone electrophoresis using a chiral crown ether , 1994 .

[36]  J. F. Stoddart,et al.  Cyclobis(paraquat-p-phenylene) as a synthetic receptor for electron-rich aromatic compounds: electrochemical and spectroscopic studies of neurotransmitter binding , 1992 .

[37]  F. Erni,et al.  Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis , 1992 .

[38]  J Hoflack,et al.  Modeling of G-protein-coupled receptors: application to dopamine, adrenaline, serotonin, acetylcholine, and mammalian opsin receptors. , 1992, Journal of medicinal chemistry.

[39]  T. H. Webb,et al.  Chemistry of synthetic receptors and functional group arrays. 16. Enantioselective and diastereoselective molecular recognition of alicyclic substrates in aqueous media by a chiral, resolved synthetic receptor , 1991 .

[40]  Anthony P. Davis,et al.  Künstliche Rezeptoren für Kohlenhydratderivate , 1990 .

[41]  A. P. Davis,et al.  Artificial Receptors for Carbohydrate Derivatives , 1990 .

[42]  H. Schneider,et al.  A Synthetic Allosteric System with High Cooperativity between Polar and Hydrophobia Binding Sites , 1990 .

[43]  H. Schneider,et al.  Ein synthetisches allosterisches System mit hoher Kooperativität zwischen polaren und hydrophoben Bindungszentren , 1990 .

[44]  M. Newcomb,et al.  Macrocycles Containing Tin. The Preparation of Macrobicyclic Lewis Acidic Hosts Containing Two Tin Atoms and 119-Sn NMR Studies of Their Chloride and Bromide Binding Properties in Solution , 1989 .

[45]  H. Schneider,et al.  Host-guest chemistry. 14. Solvent and salt effects on binding constants of organic substrates in macrocyclic host compounds. A general equation measuring hydrophobic binding contributions , 1988 .

[46]  F. Schmidtchen.  [Synthesis and binding characteristics of an artificial receptor for biogenic amines]. , 1987, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[47]  E. Kimura,et al.  A CATECHOL RECEPTOR MODEL BY MACROCYCLIC POLYAMINES , 1983 .

[48]  J. Behr,et al.  Molecular Receptors. Structural Effects and Substrate Recognition in Binding of Organic and Biogenic Ammonium Ions by Chiral Polyfunctional Macrocyclic Polyethers Bearing Amino‐Acid and Other Side‐Chains , 1982 .

[49]  E. Negishi,et al.  Selective carbon-carbon bond formation via transition metal catalysis. 3. A highly selective synthesis of unsymmetrical biaryls and diarylmethanes by the nickel- or palladium-catalyzed reaction of aryl- and benzylzinc derivatives with aryl halides , 1977 .

[50]  E. Corey,et al.  Selective formation of carbon-carbon bonds between unlike groups using organocopper reagents , 1967 .

[51]  H. Gilman,et al.  HYDROXYBENZENEBORONIC ACIDS AND ANHYDRIDES , 1957 .

[52]  M. Bock,et al.  Chapter 20. Toward the development of α1a adrenergic receptor antagonists , 2000 .

[53]  James H. R. Tucker,et al.  Electrochemical detection of catechol and dopamine as their phenylboronate ester derivatives , 2000 .

[54]  D. Barnett,et al.  The rational use of beta-adrenoceptor blockers in the treatment of heart failure. The changing face of an old therapy. , 2000, British journal of clinical pharmacology.

[55]  Q. Fernaǹdo,et al.  Molecular recognition of phenethylamine, tyramine and dopamine with new anionic cyclophanes in aqueous media , 1997 .

[56]  O. Niwa,et al.  Interdigitated array microelectrodes as electrochemical sensors , 1997 .

[57]  F. Diederich,et al.  Selective complexation of disaccharides by a novel D2-symmetrical receptor in protic solvent mixtures , 1996 .

[58]  H. Schneider.  Linear free energy relationships and pairwise interactions in supramolecular chemistry , 1994 .

[59]  P. Scrimin,et al.  A water-soluble tweezers-like metalloreceptor: binding and selective catalytic properties , 1991 .

[60]  M. P. Yeh,et al.  Preparation and Reactions of Functionalized Benzylic Organometallics of Zinc And Copper , 1990 .

[61]  H. Fujimura,et al.  Synthesis and selective molecular recognition of a macrotricyclic receptor having crown ether and cyclophane subunits as binding sites , 1990 .

[62]  H. Schneider,et al.  Large binding constant differences between aromatic and aliphatic substrates in positively charged cavities indicative of higher order electric effects , 1989 .

[63]  A. Goldblum,et al.  Acylphosphonic acids and methyl hydrogen acylphosphonates: physical and chemical properties and theoretical calculations , 1989 .

[64]  K. Kanematsu,et al.  Synthesis and characterization of crowned 1,4-benzoquinones as ionophore-dienophile (redox) combined systems: double interaction with catecholamines and tryptamine , 1988 .

[65]  J. Lehn,et al.  Polyaza macrobicyclic cryptands: synthesis, crystal structures of a cyclophane type macrobicyclic cryptand and of its dinuclear copper(I) cryptate, and anion binding features , 1987 .

[66]  M. Kodama,et al.  A new ditopic receptor molecule for ionic guest molecules , 1986 .

[67]  M. Kubo,et al.  A Novel Cyclophane. Host–Guest Complexation and Selective Inclusion of Aromatic Guests from Nonaqueous Solution , 1986 .

[68]  J. Lehn,et al.  Binding of acetylcholine and other molecular cations by a macrocyclic receptor molecule of speleand type , 1984 .

[69]  H. Whitlock,et al.  Regiospecific synthesis of islandicin methyl ether , 1980 .

[70]  H. Sterk,et al.  Über Heterocyclen, 8. Mitt.: Über 6,6′-Spirobis-(2-oxo-bzw. 2-thionohexa-hydropyrimidine) , 1966 .