Analogues of deltorphin I containing conformationally restricted amino acids in position 2: structure and opioid activity |
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| Authors: | Anika Lasota Oliwia Frączak Anna Leśniak Adriana Muchowska Michał Nowakowski Andrzej Ejchart Aleksandra Olma |
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| Affiliation: | 1. Institute of Organic Chemistry, Lodz University of Technology, Lodz, Poland;2. Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland;3. Centre of New Technologies, University of Warsaw, Warsaw, Poland;4. Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland |
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| Abstract: | New analogues of deltorphin I (DT I, Tyr‐d ‐Ala‐Phe‐Asp‐Val‐Val‐Gly‐NH2), with the d ‐Ala residue in position 2 replaced by α‐methyl‐β‐azido(amino, 1‐pyrrolidinyl, 1‐piperidinyl or 4‐morpholinyl)alanine, were synthesized by a combination of solid‐phase and solution methods. All ten new analogues were tested for receptor affinity and selectivity to μ‐ and δ‐opioid receptors. The affinity of analogues containing (R) or (S)‐α‐methyl‐β‐azidoalanine in position 2 to δ‐receptors strongly depended on the chirality of the α,α‐disubstituted residue. Peptide II , containing (S)‐α‐methyl‐β‐azidoalanine in position 2, displayed excellent δ‐receptor selectivity with its δ‐receptor affinity being only three times lower than that of DT I. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. |
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| Keywords: | α ,α ‐disubstituted glycines deltorphin I analogues opioid peptides opioid activities |
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