Synthesis and receptor binding of opioid peptide analogues containing beta3-homo-amino acids.
beta-Amino acids containing hybrid peptides and beta-peptides show great potential as peptidomimetics. In this paper we describe the synthesis and affinity toward the micro- and delta-opioid receptors of beta-peptides, analogues of Leu-enkephalin, deltorphin I, dermorphin and alpha,beta-hybrides, analogues of deltorphin I. Substitution of alpha-amino acid residues with beta(3)-homo-amino acid residues, in general resulted in decrease of affinity to opioid receptors. However, the incorporation beta(3)h-D-Ala in position 2 or beta(3)hPhe in position 3 of deltorphin I resulted in potent and selective ligand for delta-opioid receptor. The NMR studies of beta-deltorphin I analogue suggest that conformational motions in the central part of the peptide backbone are partially restricted and some conformational preferences can be expected.
Institute of Organic Chemistry, Technical University of Łódź, Zeromskiego 116, 90-924 Łódź, Poland.
Dominika
D
Wilczyńska
Piotr
P
Kosson
Maria
M
Kwasiborska
Andrzej
A
Ejchart
Aleksandra
A
Olma
D004743:Enkephalin, Leucine / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D018847:Opioid Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011957:Receptors, Opioid / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D017480:Receptors, sigma; C060208:deltorphin I, Ala(2)-; C030058:dermorphin; D004743:Enkephalin, Leucine