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 language | English (US) |
|---|---|
| Pages (from-to) | 10321-10324 |
| Number of pages | 4 |
| Journal | Journal of the American Chemical Society |
| Volume | 134 |
| Issue number | 25 |
| DOIs | |
| State | Published - Jun 27 2012 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - 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
AU - Albada, H. Bauke
AU - Wieberneit, Florian
AU - Dijkgraaf, Ingrid
AU - Harvey, Jessica H.
AU - Whistler, Jennifer
AU - Stoll, Raphael
AU - Metzler-Nolte, Nils
AU - Fish, Richard H.
PY - 2012/6/27
Y1 - 2012/6/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84863494317&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863494317&partnerID=8YFLogxK
U2 - 10.1021/ja303010k
DO - 10.1021/ja303010k
M3 - Article
C2 - 22671299
AN - SCOPUS:84863494317
VL - 134
SP - 10321
EP - 10324
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 25
ER -