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Synthesis and evaluation of derivatives of leucine enkephalin as potential affinity labels for δ opioid receptors
- Source :
- Biopolymers. 71:552-557
- Publication Year :
- 2003
- Publisher :
- Wiley, 2003.
-
Abstract
- As part of an effort to develop peptide-based affinity labels for opioid receptors, [Leu(5)]enkephalin (LeuEnk) and DTLET (Tyr-D-Thr-Gly-Phe-Leu-Thr), potent agonists for delta receptors, were selected as the parent peptides for further modification. The affinity label derivatives were prepared using standard Fmoc solid-phase peptide synthesis in conjunction with Fmoc-Phe(p-NHAlloc) (Fmoc: 9-flourenylmethoxycarbonyl;) and selective modification of the p-amino group on this residue. The electrophilic isothiocyanate and bromoacetamide groups were introduced into the para position of Phe(4); the corresponding free amine-containing peptides were also prepared for comparison. The pure peptides were evaluated in radioligand binding assays using Chinese hamster ovary (CHO) cells expressing delta and micro opioid receptors. Modification of Phe(4) in LeuEnk and DTLET significantly decreased delta-receptor binding affinity (40 to >2,000-fold). Among the synthesized analogues, [Phe(p-NH(2))(4)]DTLET showed the highest delta-receptor binding affinity (IC(50) = 39 nM) and enhanced selectivity for delta receptors compared to DTLET while other derivatives exhibited much lower delta receptor affinity. The differences in affinities between the two series of analogues and between the derivatives of LeuEnk and N,N-dibenzyl[Leu(5)]Enk reported previously suggest subtle differences in interactions of Phe(4) with delta receptors depending on other modifications in the sequences.
- Subjects :
- Enkephalin
Stereochemistry
Affinity label
Receptors, Opioid, mu
Biophysics
Peptide
CHO Cells
Biochemistry
Biomaterials
δ-opioid receptor
Radioligand Assay
chemistry.chemical_compound
Cricetinae
Receptors, Opioid, delta
Peptide synthesis
Animals
Receptor
Opioid peptide
chemistry.chemical_classification
Staining and Labeling
biology
Organic Chemistry
Affinity Labels
General Medicine
chemistry
biology.protein
Enkephalin, Leucine
Subjects
Details
- ISSN :
- 00063525
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Biopolymers
- Accession number :
- edsair.doi.dedup.....1333f7626d8f9f93d0db8b7adbc3ccf3