Solid phase synthesis and application of labeled peptide derivatives

Probes of receptor-opioid peptide interactions

Jane V. Aldrich, Vivek Kumar, Bhaswati Dattachowdhury, Angela M. Peck, Xin Wang, Thomas F. Murray

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 languageEnglish
Pages (from-to)315-321
Number of pages7
JournalInternational Journal of Peptide Research and Therapeutics
Volume14
Issue number4
DOIs
StatePublished - Dec 2008

Fingerprint

Solid-Phase Synthesis Techniques
Opioid Peptides
Peptides
Derivatives
Affinity Labels
Labels
Opioid Receptors
Peptide Receptors
Cyclization
Biotin
Pharmacology
Ligands

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 journalArticle

Aldrich, Jane V. ; Kumar, Vivek ; Dattachowdhury, Bhaswati ; Peck, Angela M. ; Wang, Xin ; Murray, Thomas F. / Solid phase synthesis and application of labeled peptide derivatives : Probes of receptor-opioid peptide interactions. In: International Journal of Peptide Research and Therapeutics. 2008 ; Vol. 14, No. 4. pp. 315-321.
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