| Title : A new class of compounds, peptide derivatives of adenosine 5'-carboxylic acid, includes inhibitors of ATP receptor-mediated responses - Uri_1994_Bioorg.Med.Chem_2_1099 |
| Author(s) : Uri A , Jarlebark L , von Kugelgen I , Schonberg T , Unden A , Heilbronn E |
| Ref : Bioorganic & Medicinal Chemistry , 2 :1099 , 1994 |
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Abstract :
A new type of ligand for the study of P2-purinergic receptor subtypes was synthesized by combining and modifying conventional nucleoside chemistry with Fmoc solid phase peptide synthesis techniques. The tri- and tetra-aspartic acid derivatives of adenosine-5'-carboxylic acid (AdoCAsp3 and AdoCAsp4) were found to act as weak agonists at P2-purinergic receptors, (activated by ATP and UTP respectively) present on C6 glioma cells. AdoCAsp4 induced inositol 1,4,5-trisphosphate formation in the C6 cells with an EC50 of 73 microM. In addition, AdoCAsp4 was found to inhibit (IC50 approximately 80 microM) ATP-induced cytosolic [Ca2+] transients in these glioma cells. The glycine derivative, AdoCGly, increased evoked release of noradrenaline from mouse vas deferens slices, probably due to the blockade of presynaptic P2-autoreceptors. The possibility that aspartic, glutamic or gamma-carboxyglutamic residues may be used to replace phosphate groups on an ATP receptor ligand, opens up new ways in ligand design. |
| PubMedSearch : Uri_1994_Bioorg.Med.Chem_2_1099 |
| PubMedID: 7773627 |
Uri A, Jarlebark L, von Kugelgen I, Schonberg T, Unden A, Heilbronn E (1994)
A new class of compounds, peptide derivatives of adenosine 5'-carboxylic acid, includes inhibitors of ATP receptor-mediated responses
Bioorganic & Medicinal Chemistry
2 :1099
Uri A, Jarlebark L, von Kugelgen I, Schonberg T, Unden A, Heilbronn E (1994)
Bioorganic & Medicinal Chemistry
2 :1099