In 2002 Saito isolated from the fungus Ctenomyces serratus the novel KOR antagonist CJ-15,208 (1), c[Phe-pro-Phe-Trp], Ki = 29 nM. In 2009, Dolle synthesized the diastereoisomer c[Phe-pro-Phe-trp], nearly 8fold more active. These compounds exhibited no agonism in vitro, however Aldrich observed unexpected MOR agonism in vivo for 1 and derivatives. These compounds show pronounced similarity with c[Phe-Gly-Tyr-pro-trp] (2), Ki(MOR) = 34 nM synthesized by a completely different approach. The sequence Ac-trp-Phe-GlyNH2 still maintains nanomolar affinity, high MOR selectivity, and the agonist behavior. Apparently, the Trp-Phe sequence represent a pharmacoric motif for both 1 and 2.1 In this work we investigate the pharmacological profile and 3D structures of peptides containing overlapping portions of 1 and 2. This analysis led to the proposal of plausible bioactive conformations.

Opioid activity profiles of peptides containing overlapping portions of CJ-15,208 and CycloEM, and identification of the bioactive conformations / R. De Marco; E. Pirazzoli; L. Cavina; A. Tolomelli; A. Bedini; S. Spampinato; R. Artali; L. Gentilucci. - STAMPA. - (2013), pp. O8-O8. (Intervento presentato al convegno EOC 2013 tenutosi a Guildford nel 10 04 2013).

Opioid activity profiles of peptides containing overlapping portions of CJ-15,208 and CycloEM, and identification of the bioactive conformations

DE MARCO, ROSSELLA;TOLOMELLI, ALESSANDRA;BEDINI, ANDREA;SPAMPINATO, SANTI MARIO;GENTILUCCI, LUCA
2013

Abstract

In 2002 Saito isolated from the fungus Ctenomyces serratus the novel KOR antagonist CJ-15,208 (1), c[Phe-pro-Phe-Trp], Ki = 29 nM. In 2009, Dolle synthesized the diastereoisomer c[Phe-pro-Phe-trp], nearly 8fold more active. These compounds exhibited no agonism in vitro, however Aldrich observed unexpected MOR agonism in vivo for 1 and derivatives. These compounds show pronounced similarity with c[Phe-Gly-Tyr-pro-trp] (2), Ki(MOR) = 34 nM synthesized by a completely different approach. The sequence Ac-trp-Phe-GlyNH2 still maintains nanomolar affinity, high MOR selectivity, and the agonist behavior. Apparently, the Trp-Phe sequence represent a pharmacoric motif for both 1 and 2.1 In this work we investigate the pharmacological profile and 3D structures of peptides containing overlapping portions of 1 and 2. This analysis led to the proposal of plausible bioactive conformations.
2013
Programme and Abstracts
O8
O8
Opioid activity profiles of peptides containing overlapping portions of CJ-15,208 and CycloEM, and identification of the bioactive conformations / R. De Marco; E. Pirazzoli; L. Cavina; A. Tolomelli; A. Bedini; S. Spampinato; R. Artali; L. Gentilucci. - STAMPA. - (2013), pp. O8-O8. (Intervento presentato al convegno EOC 2013 tenutosi a Guildford nel 10 04 2013).
R. De Marco; E. Pirazzoli; L. Cavina; A. Tolomelli; A. Bedini; S. Spampinato; R. Artali; L. Gentilucci
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/397126
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