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 language | English |
|---|---|
| Pages (from-to) | 40-45 |
| Number of pages | 6 |
| Journal | Journal of Peptide Research |
| Volume | 61 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2003 |
| Externally published | Yes |
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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 journal › Article
}
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.
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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
VL - 61
SP - 40
EP - 45
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
IS - 1
ER -