- Synthesis of tripeptides containing d-Trp substituted at the indole ring, assessment of opioid receptor binding and in vivo central antinociception
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The noncationizable tripeptide Ac-d-Trp-Phe-GlyNH2 was recently proposed as a novel minimal recognition motif for μ-opioid receptor. The introduction of different substituents (methyl, halogens, nitro, etc.) at the indole of d-Trp significantly influenced receptor affinities and resulted in serum stability and in a measurable effect on central antinociception in mice after ip administration.
- De Marco, Rossella,Bedini, Andrea,Spampinato, Santi,Gentilucci, Luca
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p. 6861 - 6866
(2014/10/15)
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- Opioid activity profiles of oversimplified peptides lacking in the protonable N-terminus
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Recently, we described cyclopeptide opioid agonists containing the D-Trp-Phe sequence. To expand the scope of this atypical pharmacophore, we tested the activity profiles of the linear peptides Ac-Xaa-Phe-Yaa (Xaa = L/D-Trp, D-His/Lys/Arg; Yaa = H, GlyNH2). Ac-D-Trp-PheNH2 appeared to be the minimal binding sequence, while Ac-D-Trp-Phe-GlyNH 2 emerged as the first noncationizable short peptide (partial) agonist with high μ-opioid receptor affinity and selectivity. Conformational analysis suggested that 5 adopts in solution a β-turn conformation.
- De Marco, Rossella,Tolomelli, Alessandra,Spampinato, Santi,Bedini, Andrea,Gentilucci, Luca
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p. 10292 - 10296
(2013/01/16)
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