An affinity label for δ-opioid receptors derived from [D-Ala 2]deltorphin I

J. V. Aldrich, H. Choi, Thomas F. Murray

Research output: Contribution to journalArticle

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Abstract

A series of potential affinity label derivatives of the amphibian opioid peptide [D-Ala2]deltorphin I were prepared by incorporation at the para position of Phe3 (in the 'message' sequence) or Phe5 (in the 'address' sequence) of an electrophilic group (i.e. isothiocyanate or bromoacetamide). The introduction of the electrophile was accomplished by incorporating Fmoc-Phe (p-NHAlloc) into the peptide, followed later in the synthesis by selective deprotection of the Alloc group and modification of the resulting amine. While para substitution decreased the δ-opioid receptor affinity, selected analogs retained nanomolar affinity for δ receptors. [D-Ala2,Phe(p-NCS)3]deltorphin I exhibited moderate affinity (IC50 = 83 nM) and high selectivity for δ receptors, while the corresponding amine and bromoacetamide derivatives showed pronounced decreases in δ-receptor affinity (80- and >1200-fold, respectively, compared with [D-Ala2]deltorphin I). In the 'address' sequence, the Phe(p-NH2)5 derivative showed the highest δ-receptor affinity (IC50 = 32 nM), while the Phe(p-NHCOCH 2Br)5 and Phe(p-NCS)5 peptides displayed four- and tenfold lower δ-receptor affinities, respectively. [D-Ala 2,Phe(p-NCS)3]deltorphin I exhibited wash-resistant inhibition of [3H][D-Pen2,D-Pen5]enkephalin (DPDPE) binding to δ receptors at a concentration of 80 nM. [D-Ala 2, Phe(p-NCS)3]deltorphin I represents the first affinity label derivative of one of the potent and selective amphibian opioid peptides, and the first electrophilic affinity label derivative of an agonist containing the reactive functionality in the 'message' sequence of the peptide.

Original languageEnglish
Pages (from-to)108-115
Number of pages8
JournalJournal of Peptide Research
Volume63
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

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Affinity Labels
Opioid Receptors
Derivatives
Opioid Peptides
Amphibians
Peptides
Inhibitory Concentration 50
Amines
D-Penicillamine (2,5)-Enkephalin
Substitution reactions
Ala(2)-deltorphin I

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

Cite this

An affinity label for δ-opioid receptors derived from [D-Ala 2]deltorphin I. / Aldrich, J. V.; Choi, H.; Murray, Thomas F.

In: Journal of Peptide Research, Vol. 63, No. 2, 02.2004, p. 108-115.

Research output: Contribution to journalArticle

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