Abstract
Solid phase synthetic methodology has been developed in our laboratory to incorporate an affinity label (a reactive functionality such as isothiocyanate or bromoacetamide) into peptides (Leelasvatanakij and Aldrich J Peptide Res 56, 80, 2000), and we have used this synthetic strategy to prepare affinity label derivatives of a variety of opioid peptides. To date side reactions have been detected only in two cases, both involving intramolecular cyclization. We have identified several peptide-based affinity labels for δ opioid receptors that exhibit wash-resistant inhibition of binding to these receptors and are valuable pharmacological tools to study opioid receptors. Even in cases where the peptide derivatives do not bind covalently to their target receptor, studying their binding has revealed subtle differences in receptor interactions with particular opioid peptide residues, especially Phe residues in the N-terminal "message" sequences. Solid phase synthetic methodology for the incorporation of other labels (e.g. biotin) into the C-terminus of peptides has also been developed in our laboratory (Kumar and Aldrich Org Lett 5, 613, 2003). These two synthetic approaches have been combined to prepare peptides containing multiple labels that can be used as tools to study peptide ligand-receptor interactions. These solid phase synthetic methodologies are versatile strategies that are applicable to the preparation of labeled peptides for a variety of targets in addition to opioid receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 315-321 |
| Number of pages | 7 |
| Journal | International Journal of Peptide Research and Therapeutics |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 2008 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Bioengineering
- Molecular Medicine
- Drug Discovery
- Analytical Chemistry
Cite this
Solid phase synthesis and application of labeled peptide derivatives : Probes of receptor-opioid peptide interactions. / Aldrich, Jane V.; Kumar, Vivek; Dattachowdhury, Bhaswati; Peck, Angela M.; Wang, Xin; Murray, Thomas F.
In: International Journal of Peptide Research and Therapeutics, Vol. 14, No. 4, 12.2008, p. 315-321.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Solid phase synthesis and application of labeled peptide derivatives
T2 - Probes of receptor-opioid peptide interactions
AU - Aldrich, Jane V.
AU - Kumar, Vivek
AU - Dattachowdhury, Bhaswati
AU - Peck, Angela M.
AU - Wang, Xin
AU - Murray, Thomas F.
PY - 2008/12
Y1 - 2008/12
N2 - Solid phase synthetic methodology has been developed in our laboratory to incorporate an affinity label (a reactive functionality such as isothiocyanate or bromoacetamide) into peptides (Leelasvatanakij and Aldrich J Peptide Res 56, 80, 2000), and we have used this synthetic strategy to prepare affinity label derivatives of a variety of opioid peptides. To date side reactions have been detected only in two cases, both involving intramolecular cyclization. We have identified several peptide-based affinity labels for δ opioid receptors that exhibit wash-resistant inhibition of binding to these receptors and are valuable pharmacological tools to study opioid receptors. Even in cases where the peptide derivatives do not bind covalently to their target receptor, studying their binding has revealed subtle differences in receptor interactions with particular opioid peptide residues, especially Phe residues in the N-terminal "message" sequences. Solid phase synthetic methodology for the incorporation of other labels (e.g. biotin) into the C-terminus of peptides has also been developed in our laboratory (Kumar and Aldrich Org Lett 5, 613, 2003). These two synthetic approaches have been combined to prepare peptides containing multiple labels that can be used as tools to study peptide ligand-receptor interactions. These solid phase synthetic methodologies are versatile strategies that are applicable to the preparation of labeled peptides for a variety of targets in addition to opioid receptors.
AB - Solid phase synthetic methodology has been developed in our laboratory to incorporate an affinity label (a reactive functionality such as isothiocyanate or bromoacetamide) into peptides (Leelasvatanakij and Aldrich J Peptide Res 56, 80, 2000), and we have used this synthetic strategy to prepare affinity label derivatives of a variety of opioid peptides. To date side reactions have been detected only in two cases, both involving intramolecular cyclization. We have identified several peptide-based affinity labels for δ opioid receptors that exhibit wash-resistant inhibition of binding to these receptors and are valuable pharmacological tools to study opioid receptors. Even in cases where the peptide derivatives do not bind covalently to their target receptor, studying their binding has revealed subtle differences in receptor interactions with particular opioid peptide residues, especially Phe residues in the N-terminal "message" sequences. Solid phase synthetic methodology for the incorporation of other labels (e.g. biotin) into the C-terminus of peptides has also been developed in our laboratory (Kumar and Aldrich Org Lett 5, 613, 2003). These two synthetic approaches have been combined to prepare peptides containing multiple labels that can be used as tools to study peptide ligand-receptor interactions. These solid phase synthetic methodologies are versatile strategies that are applicable to the preparation of labeled peptides for a variety of targets in addition to opioid receptors.
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UR - http://www.scopus.com/inward/citedby.url?scp=57349085149&partnerID=8YFLogxK
U2 - 10.1007/s10989-008-9144-1
DO - 10.1007/s10989-008-9144-1
M3 - Article
AN - SCOPUS:57349085149
VL - 14
SP - 315
EP - 321
JO - International Journal of Peptide Research and Therapeutics
JF - International Journal of Peptide Research and Therapeutics
SN - 1573-3149
IS - 4
ER -