New potent biphalin analogues containing p-fluoro-L-phenylalanine at the 4,4' positions and non-hydrazine linkers |
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Authors: | Mollica Adriano Pinnen Francesco Feliciani Federica Stefanucci Azzurra Lucente Gino Davis Peg Porreca Frank Ma Shou-Wu Lai Josephine Hruby Victor J |
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Institution: | (1) Dipartimento di Scienze del Farmaco, Universit? di Chieti-Pescara “G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy;(2) Istituto di Chimica Biomolecolare (CNR) c/o Dipartimento di Chimica e Tecnologie del Farmaco, “Sapienza”, Universit? di Roma, P.le A.Moro, 00185 Rome, Italy;(3) Department of Pharmacology, University of Arizona, Tucson, AZ 85719, USA;(4) Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA |
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Abstract: | We report the synthesis and the biological evaluation of two new analogues of the potent dimeric opioid peptide biphalin.
The performed modification is based on the replacement of two key structural elements of the native biphalin, namely: the
hydrazine bridge which joins the two palindromic moieties and the phenylalanine residues at the 4,4′ positions of the backbone.
The new analogues 9 and 10 contain 1,2-phenylenediamine and piperazine, respectively, in place of the hydrazidic linker and p-fluoro-l-phenylalanine residues at 4 and 4′ positions. Binding values are:
K\textim = 0.51 \textnM K_{\text{i}}^{\mu } = 0.51\,{\text{nM}} and
K\textid = 12.8 \textnM K_{\text{i}}^{\delta } = 12.8\,{\text{nM}} for compound 9,
K\textim = 0.09 \textnM K_{\text{i}}^{\mu } = 0.09\,{\text{nM}} and
K\textid = 0.11 \textnM K_{\text{i}}^{\delta } = 0.11\,{\text{nM}} for analogue 10. |
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