Interaction of deltorphin with opioid receptors: molecular determinants for affinity and selectivity.

Abstract:

:Opioid receptor analyses of deltorphin A (H-Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2) analogues indicated the following: (a) increased negativity differentially affected affinities (Ki) and selectivity (Ki mu/Ki delta); (b) shifted sequence heptapeptides, [Asp5,Leu6,Met-NH2(7)] and [Asp4,His5,Leu6,Met-NH2(7)], reversed selectivity (delta-->mu); (c) substitutions at positions 4, 5, and 6 diminished selectivity, with changes in residue 5 being the most detrimental; (d) C-terminal deletions differentially effected Ki. These are the first data to demonstrate a reversal of delta selectivity in heptapeptides containing a negative charge and indicate that modifications in affinity occur through changes in both anionic and hydrophobic properties of residues at specific positions in the peptide. Deltorphin analogues might also be applied to differentiate between opioid receptor subsites.

journal_name

Peptides

journal_title

Peptides

authors

Lazarus LH,Salvadori S,Attila M,Grieco P,Bundy DM,Wilson WE,Tomatis R

doi

10.1016/0196-9781(93)90006-3

subject

Has Abstract

pub_date

1993-01-01 00:00:00

pages

21-8

issue

1

eissn

0196-9781

issn

1873-5169

pii

0196-9781(93)90006-3

journal_volume

14

pub_type

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