The Synthesis of DAMGO-Based Potential Affinity Labels with High Mu Opioid Receptor Affinity and the Formation of Cyclic O-Alkyl Thiocarbamates

Dattachowdhury, Bhaswati; Murray, Thomas F.; Aldrich, Jane V.

doi:10.1007/978-0-387-73657-0_119

Cited by 1 publication

(2 citation statements)

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“…Recently we have also been exploring alternative positions for incorporation of the reactive affinity labeling group, including alternative positions on the phenyl ring of a phenylalanine residue (Wang et al, 2006) and alternative residues in the sequence (Dattachowdhury et al, 2008). The synthetic strategy has been applied successfully to peptides containing a variety of amino acids, including basic (Arg and Lys), acidic (Asp) and hydroxyl-containing (Tyr, Ser, and Thr) amino acids.…”

Section: Resultsmentioning

confidence: 99%

“…To date we have only observed side reactions in two cases, both of which involved intramolecular cyclization. One involved the C-terminal alcohol of DAMGO ([D-Ala 2 , NMePhe 4 , glyol]enkephalin) derivatives reacting with an affinity label group attached to the side chain of a D-diamino acid in position 2 (Dattachowdhury et al, 2008). While the bromoacetamide derivatives were successfully prepared, following cleavage from the resin the isothiocyanate derivatives underwent intramolecular cyclization with the C-terminal glyol to yield O-alkyl thiocarbamates.…”

Section: Resultsmentioning

confidence: 99%

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Solid Phase Synthesis and Application of Labeled Peptide Derivatives: Probes of Receptor-Opioid Peptide Interactions

Aldrich

Kumar

Dattachowdhury

et al. 2008

Int J Pept Res Ther

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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, L. and Aldrich, J. V. (2000) J. Peptide Res. 56, 80), 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, V. and Aldrich, J. V. (2003) Org. Lett. 5, 613). 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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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%