Description

• Title:
  The impact of β-azido(or 1-piperidinyl) methylamino acids in position 2 or 3 on biological activity and conformation of dermorphin analogues
• Creator:
  Maciejczyk, Maciej;
  Lasota, Anika;
  Frączak, Oliwia;
  Kosson, Piotr;
  Misicka, Aleksandra;
  Nowakowski, Michał;
  Ejchart, Andrzej;
  Olma, Aleksandra
• Description:
  The synthesis of new dermorphin analogues is described. The (R)-alanine or phenylalanine residues of natural dermorphin were substituted by the corresponding α-methyl-β-azidoalanine or α-benzyl-β-azido(1-piperidinyl)alanine residues. The potency and selectivity of the newanalogueswere evaluated by a competitive receptor binding assay in rat brain using [3H]DAMGO (a μ ligand) and [3H]DELT (a δ ligand). The most active analogue in this series, Tyr-(R)-Ala-(R)-α-benzyl-β-azidoAla-Gly-Tyr-Pro-Ser-NH2 and its epimer were analysed by 1H and 13C NMR spectroscopy and restrainedmolecular dynamics simulations. The dominant conformation of the investigated peptides depended on the absolute configuration around Cα in the α-benzyl-β-azidoAla residue in position 3. The (R) configuration led to the formation of a type I β-turn, whilst switching to the (S) configuration gave rise to an inverse β- turn of type I′, followed by the formation of a very short β-sheet. The selectivity of Tyr-(R)-Ala-(R) and (S)-α-benzyl-β-azidoAla-Gly- Tyr-Pro-Ser-NH2 was shown to be very similar; nevertheless, the two analogues exhibited different conformational preferences.
• Object availability:
  free access
• Date:
  2016.06.06
• Type:
  Article;
  PeerReviewed
• Language:
  English
• Format:
  application/msword
• Publisher:
  European Peptide Society and John Wiley & Sons, Ltd
• Relation: http://eprints.ibb.waw.pl/1279 ;http://onlinelibrary.wiley.com/doi/10.1002/psc.2903/abstract ;
  10.1002/psc.2903
• Subject:
  QD Chemistry
• Identifier: http://eprints.ibb.waw.pl/1279/1/JPS-105.docx ;
  Maciejczyk, Maciej and Lasota, Anika and Frączak, Oliwia and Kosson, Piotr and Misicka, Aleksandra and Nowakowski, Michał and Ejchart, Andrzej and Olma, Aleksandra (2016) The impact of β-azido(or 1-piperidinyl) methylamino acids in position 2 or 3 on biological activity and conformation of dermorphin analogues. Journal of Peptide Science, 22 (8). pp. 545-551. ISSN 1099-1387
• Data provider:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
• Can I use it?:
  seek permission
• Type:
  other