The chemoselective reactions of tyrosine-containing G-protein-coupled receptor peptides with [Cp*Rh(H 2O) 3](OTf) 2, including 2D NMR structures and the biological consequences

H. Bauke Albada, Florian Wieberneit, Ingrid Dijkgraaf, Jessica H. Harvey, Jennifer Whistler, Raphael Stoll, Nils Metzler-Nolte, Richard H. Fish

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The bioconjugation of organometallic complexes with peptides has proven to be a novel approach for drug discovery. We report the facile and chemoselective reaction of tyrosine-containing G-protein-coupled receptor (GPCR) peptides with [Cp*Rh(H 2O) 3](OTf) 2, in water, at room temperature, and at pH 5-6. We have focused on three important GPCR peptides; namely, [Tyr 1]-leu-enkephalin, [Tyr 4]-neurotensin(8-13), and [Tyr 3]-octreotide, each of which has a different position for the tyrosine residue, together with competing functionalities. Importantly, all other functional groups present, i.e., amino, carboxyl, disulfide, phenyl, and indole, were not prominent sites of reactivity by the Cp*Rh tris aqua complex. Furthermore, the influence of the Cp*Rh moiety on the structure of [Tyr 3]-octreotide was characterized by 2D NMR, resulting in the first representative structure of an organometallic-peptide complex. The biological consequences of these Cp*Rh-peptide complexes, with respect to GPCR binding and growth inhibition of MCF7 and HT29 cancer cells, will be presented for [(η 6-Cp*Rh-Tyr 1)-leu-enkephalin] (OTf) 2 and [(η 6-Cp*Rh-Tyr 3)- octreotide](OTf) 2.

Original languageEnglish (US)
Pages (from-to)10321-10324
Number of pages4
JournalJournal of the American Chemical Society
Volume134
Issue number25
DOIs
StatePublished - Jun 27 2012
Externally publishedYes

Fingerprint

G-Protein-Coupled Receptors
Peptides
Tyrosine
Nuclear magnetic resonance
Proteins
Leucine Enkephalin
neurotensin (8-13)
Organometallics
HT29 Cells
Drug Discovery
Disulfides
Functional groups
Cells
Hydrogen
Temperature
Water
Growth
3-Tyr-octreotide
Neoplasms

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

The chemoselective reactions of tyrosine-containing G-protein-coupled receptor peptides with [Cp*Rh(H 2O) 3](OTf) 2, including 2D NMR structures and the biological consequences. / Albada, H. Bauke; Wieberneit, Florian; Dijkgraaf, Ingrid; Harvey, Jessica H.; Whistler, Jennifer; Stoll, Raphael; Metzler-Nolte, Nils; Fish, Richard H.

In: Journal of the American Chemical Society, Vol. 134, No. 25, 27.06.2012, p. 10321-10324.

Research output: Contribution to journalArticle

Albada, H. Bauke ; Wieberneit, Florian ; Dijkgraaf, Ingrid ; Harvey, Jessica H. ; Whistler, Jennifer ; Stoll, Raphael ; Metzler-Nolte, Nils ; Fish, Richard H. / The chemoselective reactions of tyrosine-containing G-protein-coupled receptor peptides with [Cp*Rh(H 2O) 3](OTf) 2, including 2D NMR structures and the biological consequences. In: Journal of the American Chemical Society. 2012 ; Vol. 134, No. 25. pp. 10321-10324.
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