Abstract
Tyr-Tic-Phe-Phe-OH (TIPP) and the shorter Tyr-Tic-Phe-OH (TIP) peptides are potent and highly selective antagonists at the δ-opioid receptor and, therefore, are ideal candidates for the attachment of labels to assist in the study of δ-opioid receptors. Peptides extended at the C-terminus with residues which can be used as handles for further modification and/or labeling (i.e. Asx, Glx, and Lys) were synthesized. The TIPP-D/L-Asx/Glx derivatives exhibited similar δ-receptor affinity to TIPP (Ki = 5-10 nM vs Ki = 6 nM), and neither the location of the carboxylic acid moiety nor the stereochemistry of the C-terminal residue significantly affected the δ-receptor affinity of these derivatives. Extension of TIPP with an additional residue did not increase μ-receptor affinity, even though the position of the acidic group, which imparts δ-receptor selectivity to TIPP, was shifted relative to the carboxylic acid moiety of TIPP. The δ-receptor affinities of the TIP-D/L-Asx/Glx derivatives were found to be influenced mainly by the position of the carboxylic acid function rather than the stereochemistry of the C-terminal residue. TIP(P)-D/L-Lys(Ac)-OH derivatives exhibited, moderate δ-receptor affinity (Ki δ = 16-28 nM). The most potent compounds found in the extended TIP(P) series were TIPP-D-Gln-OH and TIP-D-Gln-OH (Ki δ = 5 nM) which had similar affinities to TIPP.
| Original language | English |
|---|---|
| Pages (from-to) | 5050-5054 |
| Number of pages | 5 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 43 |
| Issue number | 26 |
| DOIs | |
| State | Published - Dec 28 2000 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Organic Chemistry
Cite this
Extended TIP(P) analogues as precursors for labeled δ-opioid receptor ligands. / Kumar, V.; Murray, Thomas F.; Aldrich, J. V.
In: Journal of Medicinal Chemistry, Vol. 43, No. 26, 28.12.2000, p. 5050-5054.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Extended TIP(P) analogues as precursors for labeled δ-opioid receptor ligands
AU - Kumar, V.
AU - Murray, Thomas F.
AU - Aldrich, J. V.
PY - 2000/12/28
Y1 - 2000/12/28
N2 - Tyr-Tic-Phe-Phe-OH (TIPP) and the shorter Tyr-Tic-Phe-OH (TIP) peptides are potent and highly selective antagonists at the δ-opioid receptor and, therefore, are ideal candidates for the attachment of labels to assist in the study of δ-opioid receptors. Peptides extended at the C-terminus with residues which can be used as handles for further modification and/or labeling (i.e. Asx, Glx, and Lys) were synthesized. The TIPP-D/L-Asx/Glx derivatives exhibited similar δ-receptor affinity to TIPP (Ki = 5-10 nM vs Ki = 6 nM), and neither the location of the carboxylic acid moiety nor the stereochemistry of the C-terminal residue significantly affected the δ-receptor affinity of these derivatives. Extension of TIPP with an additional residue did not increase μ-receptor affinity, even though the position of the acidic group, which imparts δ-receptor selectivity to TIPP, was shifted relative to the carboxylic acid moiety of TIPP. The δ-receptor affinities of the TIP-D/L-Asx/Glx derivatives were found to be influenced mainly by the position of the carboxylic acid function rather than the stereochemistry of the C-terminal residue. TIP(P)-D/L-Lys(Ac)-OH derivatives exhibited, moderate δ-receptor affinity (Ki δ = 16-28 nM). The most potent compounds found in the extended TIP(P) series were TIPP-D-Gln-OH and TIP-D-Gln-OH (Ki δ = 5 nM) which had similar affinities to TIPP.
AB - Tyr-Tic-Phe-Phe-OH (TIPP) and the shorter Tyr-Tic-Phe-OH (TIP) peptides are potent and highly selective antagonists at the δ-opioid receptor and, therefore, are ideal candidates for the attachment of labels to assist in the study of δ-opioid receptors. Peptides extended at the C-terminus with residues which can be used as handles for further modification and/or labeling (i.e. Asx, Glx, and Lys) were synthesized. The TIPP-D/L-Asx/Glx derivatives exhibited similar δ-receptor affinity to TIPP (Ki = 5-10 nM vs Ki = 6 nM), and neither the location of the carboxylic acid moiety nor the stereochemistry of the C-terminal residue significantly affected the δ-receptor affinity of these derivatives. Extension of TIPP with an additional residue did not increase μ-receptor affinity, even though the position of the acidic group, which imparts δ-receptor selectivity to TIPP, was shifted relative to the carboxylic acid moiety of TIPP. The δ-receptor affinities of the TIP-D/L-Asx/Glx derivatives were found to be influenced mainly by the position of the carboxylic acid function rather than the stereochemistry of the C-terminal residue. TIP(P)-D/L-Lys(Ac)-OH derivatives exhibited, moderate δ-receptor affinity (Ki δ = 16-28 nM). The most potent compounds found in the extended TIP(P) series were TIPP-D-Gln-OH and TIP-D-Gln-OH (Ki δ = 5 nM) which had similar affinities to TIPP.
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UR - http://www.scopus.com/inward/citedby.url?scp=0034727863&partnerID=8YFLogxK
U2 - 10.1021/jm000362h
DO - 10.1021/jm000362h
M3 - Article
C2 - 11150177
AN - SCOPUS:0034727863
VL - 43
SP - 5050
EP - 5054
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 26
ER -