Dermorphin-based potential affinity labels for μ-opioid receptors

H. Choi, Thomas F. Murray, Jane V. Aldrich

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Dermorphin and [Lys7]dermorphin, selective μ-opioid receptor ligands originating from amphibian skin, have been modified with various electrophiles in either the 'message' or 'address' sequences as potential peptide-based affinity labels for μ-receptors. Introduction of the electrophilic isothiocyanate and bromoacetamide groups on the para position of Phe3 and Phe5 was accomplished by incorporating Fmoc-Phe(p-NHAlloc) into the peptide followed by selective deprotection and modification. The corresponding amine-containing peptides were also prepared. The pure peptides were evaluated in radioligand binding experiments using Chinese hamster ovary (CHO) cells expressing μ- and δ-opioid receptors. In dermorphin, introduction of the electrophilic groups in the 'message' domain lowered the binding affinity by > 1000-fold; only [Phe(p-NH2)3]dermorphin retained nanomolar affinity for μ-receptors. Modifications in the 'address' region of both dermorphin and [Lys7]dermorphin were relatively well tolerated. In particular, [Phe(p-NH2)5, Lys7]dermorphin showed similar affinity to dermorphin, with almost 2-fold higher selectivity for μ-receptors. [Phe(p-NHCOCH2Br)5]- and [Phe(p-NHCOCH2Br)5, Lys7]dermorphin exhibited relatively high affinity (IC50 = 27.7 and 15.1 nM, respectively) for μ-receptors. However, neither of these peptides inhibited [3H]DAMGO binding in a wash-resistant manner.

Original languageEnglish
Pages (from-to)40-45
Number of pages6
JournalJournal of Peptide Research
Volume61
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Affinity Labels
Opioid Receptors
Peptides
Ala(2)-MePhe(4)-Gly(5)-enkephalin
dermorphin
Amphibians
Cricetulus
Inhibitory Concentration 50
Amines
Ovary
Skin
Cells
Ligands

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

Cite this

Dermorphin-based potential affinity labels for μ-opioid receptors. / Choi, H.; Murray, Thomas F.; Aldrich, Jane V.

In: Journal of Peptide Research, Vol. 61, No. 1, 01.01.2003, p. 40-45.

Research output: Contribution to journalArticle

@article{39a11a33dd47476eae8b3675dec3b435,
title = "Dermorphin-based potential affinity labels for μ-opioid receptors",
abstract = "Dermorphin and [Lys7]dermorphin, selective μ-opioid receptor ligands originating from amphibian skin, have been modified with various electrophiles in either the 'message' or 'address' sequences as potential peptide-based affinity labels for μ-receptors. Introduction of the electrophilic isothiocyanate and bromoacetamide groups on the para position of Phe3 and Phe5 was accomplished by incorporating Fmoc-Phe(p-NHAlloc) into the peptide followed by selective deprotection and modification. The corresponding amine-containing peptides were also prepared. The pure peptides were evaluated in radioligand binding experiments using Chinese hamster ovary (CHO) cells expressing μ- and δ-opioid receptors. In dermorphin, introduction of the electrophilic groups in the 'message' domain lowered the binding affinity by > 1000-fold; only [Phe(p-NH2)3]dermorphin retained nanomolar affinity for μ-receptors. Modifications in the 'address' region of both dermorphin and [Lys7]dermorphin were relatively well tolerated. In particular, [Phe(p-NH2)5, Lys7]dermorphin showed similar affinity to dermorphin, with almost 2-fold higher selectivity for μ-receptors. [Phe(p-NHCOCH2Br)5]- and [Phe(p-NHCOCH2Br)5, Lys7]dermorphin exhibited relatively high affinity (IC50 = 27.7 and 15.1 nM, respectively) for μ-receptors. However, neither of these peptides inhibited [3H]DAMGO binding in a wash-resistant manner.",
author = "H. Choi and Murray, {Thomas F.} and Aldrich, {Jane V.}",
year = "2003",
month = "1",
day = "1",
doi = "10.1034/j.1399-3011.2003.20030.x",
language = "English",
volume = "61",
pages = "40--45",
journal = "Chemical Biology and Drug Design",
issn = "1747-0277",
publisher = "Blackwell",
number = "1",

}

TY - JOUR

T1 - Dermorphin-based potential affinity labels for μ-opioid receptors

AU - Choi, H.

AU - Murray, Thomas F.

AU - Aldrich, Jane V.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - Dermorphin and [Lys7]dermorphin, selective μ-opioid receptor ligands originating from amphibian skin, have been modified with various electrophiles in either the 'message' or 'address' sequences as potential peptide-based affinity labels for μ-receptors. Introduction of the electrophilic isothiocyanate and bromoacetamide groups on the para position of Phe3 and Phe5 was accomplished by incorporating Fmoc-Phe(p-NHAlloc) into the peptide followed by selective deprotection and modification. The corresponding amine-containing peptides were also prepared. The pure peptides were evaluated in radioligand binding experiments using Chinese hamster ovary (CHO) cells expressing μ- and δ-opioid receptors. In dermorphin, introduction of the electrophilic groups in the 'message' domain lowered the binding affinity by > 1000-fold; only [Phe(p-NH2)3]dermorphin retained nanomolar affinity for μ-receptors. Modifications in the 'address' region of both dermorphin and [Lys7]dermorphin were relatively well tolerated. In particular, [Phe(p-NH2)5, Lys7]dermorphin showed similar affinity to dermorphin, with almost 2-fold higher selectivity for μ-receptors. [Phe(p-NHCOCH2Br)5]- and [Phe(p-NHCOCH2Br)5, Lys7]dermorphin exhibited relatively high affinity (IC50 = 27.7 and 15.1 nM, respectively) for μ-receptors. However, neither of these peptides inhibited [3H]DAMGO binding in a wash-resistant manner.

AB - Dermorphin and [Lys7]dermorphin, selective μ-opioid receptor ligands originating from amphibian skin, have been modified with various electrophiles in either the 'message' or 'address' sequences as potential peptide-based affinity labels for μ-receptors. Introduction of the electrophilic isothiocyanate and bromoacetamide groups on the para position of Phe3 and Phe5 was accomplished by incorporating Fmoc-Phe(p-NHAlloc) into the peptide followed by selective deprotection and modification. The corresponding amine-containing peptides were also prepared. The pure peptides were evaluated in radioligand binding experiments using Chinese hamster ovary (CHO) cells expressing μ- and δ-opioid receptors. In dermorphin, introduction of the electrophilic groups in the 'message' domain lowered the binding affinity by > 1000-fold; only [Phe(p-NH2)3]dermorphin retained nanomolar affinity for μ-receptors. Modifications in the 'address' region of both dermorphin and [Lys7]dermorphin were relatively well tolerated. In particular, [Phe(p-NH2)5, Lys7]dermorphin showed similar affinity to dermorphin, with almost 2-fold higher selectivity for μ-receptors. [Phe(p-NHCOCH2Br)5]- and [Phe(p-NHCOCH2Br)5, Lys7]dermorphin exhibited relatively high affinity (IC50 = 27.7 and 15.1 nM, respectively) for μ-receptors. However, neither of these peptides inhibited [3H]DAMGO binding in a wash-resistant manner.

UR - http://www.scopus.com/inward/record.url?scp=0037228732&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037228732&partnerID=8YFLogxK

U2 - 10.1034/j.1399-3011.2003.20030.x

DO - 10.1034/j.1399-3011.2003.20030.x

M3 - Article

C2 - 12472847

AN - SCOPUS:0037228732

VL - 61

SP - 40

EP - 45

JO - Chemical Biology and Drug Design

JF - Chemical Biology and Drug Design

SN - 1747-0277

IS - 1

ER -