188259-18-9Relevant academic research and scientific papers
Tritiated deltorphin analogues with high specific radioactivity and high affinity and selectivity for delta opioid receptors
Darula, Zsuzsa,Peter, Antal,Toth, Geza
, p. 817 - 826 (1997)
New conformationally constrained deltorphin I and II analogues were designed and synthesized, using a more lipophilic amino acid (Ile) instead of Val at positions 5 and 6, and 2-aminotetralin-2-carboxylic acid (Atc) at position 3. Two analogues (Tyr-D-Ala-(S)-Atc-Asp-Ile-Ile-Gly-NH2 and Tyr-D-Ala-(R)-Atc-Glu-Ile-Ile-Gly-NH2) with high potency and selectivity for δ opioid receptors were chosen for tritiation, with 3,5-I2-Tyr1-deltorphin analogues as precursors. Catalytic dehalotritiation of these precursors resulted in tritiated peptides with high specific radioactivity (1.28 TBq/mmol (34.5 Ci/mmol) and 1.33 TBq/mmol (36.0 Ci/mmol), respectively).
Conformationally constrained deltorphin analogs with 2-aminotetralin-2- carboxylic acid in position 3
Tóth, Géza,Darula, Zsuzsa,Péter, Antal,Fül?p, Ferenc,Tourwé, Dirk,Jaspers, Hendrika,Verheyden, Patricia,B?cskey, Zsolt,Tóth, Zoltán,Borsodi, Anna
, p. 990 - 995 (2007/10/03)
Two approaches to the design of very active and highly selective δ opioid peptides were used to obtain new deltorphin analogs with altered hydrophobic and stereoelectronic properties. Deltorphin I and II analogs were synthesized involving the substitution of Ile instead of Val at positions 5 and 6 in the address domain and 2-aminotetralin-2-carboxylic acid (Atc) instead of Phe in the message domain. The peptides were agonists in the subnanomolar range in the MVD assay and in the micromolar or higher range in the GPI assay, showing a very high selectivity for δ receptors. A very similar trend could be observed in radioreceptor binding assays in which selective tritiated opioid ligands were used. (R)- and (S)-Atc-deltorphins exhibited similar K(i) values in the binding assay, with almost complete loss of the stereospecificity of the binding. Conformational studies provided evidence for little disturbance of the backbone conformational equilibrium when Phe3 is replaced by (S)- or (R)-Atc. The use of the Atc constraint gives additional evidence that, during its interaction with the δ receptor, the side chain of residue 3 adopts the trans conformation at χ1.
