- Enantioselective fluorescence recognition of chiral amines by n-acyl-(s)-1-naphthylalanyl-(s)-phenylglycine and n-acyl-(s)-1-naphthylalanyl- (s)-1-naphthylalanine dipeptides bridged by a 1,2-phenylene or an ethylene spacer chain
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This study sought to support the development of enantioselective dipeptide fluorescence sensors by examining the ability of the N-acyl-(S)-1- naphthylalanyl-(S)-phenylglycine and N-acyl-(S)-1-naphthylalanyl-(S)-1- naphthylalanine dipeptides (bridged by the 1,2-phenylene or ethylene spacer chain) to discriminate between aliphatic amine-derived (S)- and (R)-enantiomers. The results indicated that both hydrogen-bonding interactions in the ground state and charge-transfer interactions in the excited state are involved in the fluorescence quenching of these bridged dipeptides by chiral amines to produce the upward curving Stern-Volmer plots. In addition, the numerical analysis of these plots led to the conclusion that the bridged naphthylalanylphenylglycine dipeptide shows the highest ability to differentiate the (S)-enantiomer from (R)-enantiomer when the emission of this dipeptide is quenched by chiral alaninols.
- Ishikawa, Tomoe,Sonobe, Miho,Hayakawa, Akinori,Igarashi, Tetsutaro,Sakurai, Tadamitsu
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p. 1039 - 1058
(2013/05/23)
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- Naphthyl-l-α-amino acids via chemo-enzymatic dynamic kinetic resolution
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A double catalyst system (protease + base) was applied to the dynamic kinetic resolution (DKR) of isomeric 1- and 2-α-naphthyl-glycines and -alanines exploiting the in situ racemization of their thioesters. Due to the different C-acidity of the two sets of compounds, different experimental conditions have been devised to perform the simultaneous resolution/racemization process. In all cases, the racemic N-Boc-thioesters were converted into the aminoacids with an l-configuration almost quantitatively and with complete enantioselectivity. 2012 Elsevier Ltd.
- D'Arrigo, Paola,Cerioli, Lorenzo,Fiorati, Andrea,Servi, Stefano,Viani, Fiorenza,Tessaro, Davide
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p. 938 - 944
(2012/10/08)
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- Antithrombotic azacycloalkylalkanoyl peptides and pseudopeptides
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The present invention relates to azacycloalkylalkanoyl peptides and pseudopeptides which inhibit platelet aggregation and thrombus formation thereby being useful in the prevention and treatment of thrombosis associated with disease states such as myocardial infarction, stroke, peripheral arterial disease, and disseminated intravascular coagulation, to methods for the prevention or treatment of thrombosis in a mammal in need of such therapy comprising the administration of a therapeutically effective amount of such compounds, and to pharmaceutical compositions comprising such compounds.
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- Synthesis and biological activity of ketomethylene pseudopeptide analogues as thrombin inhibitors
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Ketomethylene pseudopeptide analogues Aa-Pro-Argψ(COCH2)Gly-pip, 1, where Aa are D- or L-amino acids (Dpa, β,β-diphenylalanine; αNal, α- naphthylalanine; βNal, β-naphthylalanine; Fgl, fluorenylglycine) with highly lipophilic side chains and ψ(COCH2) is a ketomethylene pseudopeptide bond, have been synthesized through a modified Dakin-West reaction under very mild conditions with a high yield using tripeptide 4 with a labile functional group directly on the side chain. Their enzymatic assay of thrombin inhibition has been carried out. The structure-activity relationship study indicated that a lipophilic side chain on the amino acid in the P3 position is very important for binding to the apolar site of thrombin. Compound 1a with D-Dpa at the P3 position has a K(i) of 0.2 μM and it doubles thrombin clotting time at only 3 times higher concentration. These values are about 7 times better than those of the corresponding D-Phe analogues. Furthermore, 1a shows poor inhibitory activity against plasmin, factor Xa, urokinase, and kallikrein. Preliminary in vivo testing (3-4-kg rabbit as the animal model) shows no observable side effect (change of blood pressure and accumulation of blood platelet in lungs) at a dose of 1 mg/kg.
- Cheng,Goodwin,Schully,Kakkar,Claeson
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p. 3364 - 3369
(2007/10/02)
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- Synthesis and biological activities of cholecystokinin analogues substituted in position 30 by 3-(1-naphthyl)-L-alanine [Nal(1)] or 3-(2-naphthyl)-L-alanine [Nal(2)]
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Acetyl derivatives of ethyl esters of 3-(1-naphthyl)-D,L-alanine and 3-(2-naphthyl)-D,L-alanine were synthesized through a malonic condensation. Resolution of these derivatives by subtilisin Carlsberg followed by acid hydrolysis afforded the 2 optical isomers of 3-(1-naphthyl)-alanine [Nal(1)] and 3-(2-naphthyl)-alanine [Nal(2)]. The L enantiomers of these amino acids were incorporated into the sequence of cholecystokinin in place of the tryptophan in position 30. The cholecystokinin analogues thus obtained behaved as full agonists, with reduced potencies on rat pancreatic acini and on guinea pig brain membranes, by about one order of magnitude for the Nal(1) derivative, as compared to the potent parent compound Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-Phe-NH2.
- Rodriguez,Bernad,Galas,Lignon,Laur,Aumelas,Martinez
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p. 245 - 253
(2007/10/02)
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