New propranolol analogues: binding and chiral discrimination by cellobiohydrolase Cel7A

Fagerström, Alexandra; Nilsson, Mikael; Berg, Ulf; Isaksson, Roland

doi:10.1039/b605603b

Cited by 15 publications

(13 citation statements)

References 27 publications

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“…The use of various analytical methods for drug-protein binding measurements has been reviewed [152,153]. Recently CE has been used to measure binding of anticancer gallium(III) complexes to transferrin and serum albumin [154], novel antitumor ruthenium(III) complexes to human serum proteins [155][156][157], anticancer drugs to serum proteins [158], basic drugs to serum proteins, BSA, and a 1 -acid glyco-protein [159], theophylline to human serum albumin [160], oxindole alkaloid from Uncaria tomentosa to amyloid protein for potential treatment of Alzheimer's disease [161], new propranolol analogues to serum proteins [162], a dimeric inhibitor to 3C-like proteinase [163], roscovitine to plasma proteins [164], and drug suramin to b 2 -microglobulin [165,166]. The effect of drug complexation on stability and conformation of human serum albumin has been also studied [167].…”

Section: Protein Interactions With Other Moleculesmentioning

confidence: 99%

Capillary electrophoresis of proteins 2005–2007

Dolnı́k¹

2007

Electrophoresis

152

106

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This review article with 239 references describes recent developments in capillary electrophoresis of proteins, and covers the two years since the previous review (V. Dolník, Electrophoresis 2006, 27, 126-141) through spring 2007. It includes topics related to CE of proteins, such as sample pretreatment, wall coatings, improving separation, various forms of detection, and special electrophoretic techniques including ACE, CIEF, capillary ITP, and CEC. The paper describes applications of CE to analysis of proteins in real-world samples including human body fluids, food and agricultural samples, protein pharmaceuticals and recombinant protein preparations.

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Section: Protein Interactions With Other Moleculesmentioning

confidence: 99%

Capillary electrophoresis of proteins 2005–2007

Dolnı́k¹

2007

Electrophoresis

152

106

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“…The binding and chiral selection of adrenergic beta-blocker enantiomers by Cel7A have been studied by chromatography, electrophoresis [24,[30][31][32][33] calorimetry, [34,35] as well as their inhibitory effects on enzyme activity. [36,37] X-ray crystal structures of the catalytic module of H. jecorina Cel7A in complex with (S)-propranolol [28] and of the homologous enzyme Cel7D from Phanerochaete chrysosporium in complexw ith (R)-propranolol, [38] show that the compounds bind over subsites À1a nd + 1a t the catalytic centeri nt he active site.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Binding of Propranolol and Analogues Thereof to Cellobiohydrolase Cel7A

Hamark

Pendrill

Landström

et al. 2018

Chemistry A European J

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At the catalytic site for the hydrolysis of cellulose the enzyme cellobiohydrolase Cel7A binds the enantiomers of the adrenergic beta-blocker propranolol with different selectivity. Methyl-to-hydroxymethyl group modificationso f propranolol, which result in higher affinity andi mproveds electivity, were herein studied by 1 H, 1 Ha nd 1 H, 13 Cs calar spinspin coupling constants as well as utilizing the nuclearO verhauser effect( NOE) in conjunction with molecular dynamics simulations of the ligandsp er se, whichs howedt he presence of all-antiperiplanar conformations, except for the one containing av icinal oxygen-oxygen arrangementg overned by the gauche effect. For the ligand-protein complexes investigated by NMR spectroscopy using, inter alia, transferred NOESY and saturation-transfer difference( STD) NMR experiments the S-isomers were shown to bind with ah ighera ffin-ity and ac onformation similar to that preferred in solution, in contrastt ot he R-isomer.T he fact that the S-form of the propranolol enantiomer is pre-arrangedf or binding to the protein is also observed for ac rystals tructureo fd ihydroxy-(S)-propranolol and Cel7A presentedh erein.W hereas the binding of propranolol is entropyd riven, the complexation with the dihydroxya naloguei sa nticipated to be favored also by an enthalpic term, such as fori ts enantiomer, that is, dihydroxy-(R)-propranolol, because hydrogen-bond donation replacest he corresponding bondingf rom hydroxyl groups in glucosyl residues of the natural substrate. In addition to a favorable entropy component, albeit lesseri nm agnitude, this represents an effect of enthalpy-to-entropy compensation in ligand-protein interactions.

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“…Commercially available glycidol 15 activated as the m -nitrobenzene sulfonyl ( m -nosyl) ester 5 has previously been shown to be an ideal leaving group in reactions with aryloxy nucleophiles (e.g., 4 ) as it promotes direct S N 2 over S N 2’ attack thereby suppressing racemisation [15]. m -Nosylate 5 was synthesised by using nosyl chloride at low temperature [19]. Upon cooling, the reaction mixture became a viscous slurry, and it was important to maintain vigorous stirring to ensure full conversion.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of the calcilytic ligand NPS 2143

Johansson¹,

Cailly²,

Thomsen³

et al. 2013

Beilstein J. Org. Chem.

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Summary(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.

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New propranolol analogues: binding and chiral discrimination by cellobiohydrolase Cel7A

Cited by 15 publications

References 27 publications

Capillary electrophoresis of proteins 2005–2007

Capillary electrophoresis of proteins 2005–2007

Enantioselective Binding of Propranolol and Analogues Thereof to Cellobiohydrolase Cel7A

Synthesis of the calcilytic ligand NPS 2143

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