The Chemoselective Reactions of Tyrosine-Containing G-Protein-Coupled Receptor Peptides with [Cp*Rh(H2O)3](OTf)2, Including 2D NMR Structures and the Biological Conseq

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• 作者：H. Bauke Albada ; Florian Wieberneit ; Ingrid Dijkgraaf ; Jessica H. Harvey ; Jennifer L. Whistler ; Raphael Stoll ; Nils Metzler-Nolte ; Richard H. Fish
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：June 27, 2012
• 年：2012
• 卷：134
• 期：25
• 页码：10321-10324
• 全文大小：235K
• 年卷期：v.134,no.25(June 27, 2012)
• ISSN：1520-5126

文摘

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(H₂O)₃](OTf)₂, in water, at room temperature, and at pH 5鈥?. We have focused on three important GPCR peptides; namely, [Tyr¹]-leu-enkephalin, [Tyr⁴]-neurotensin(8-13), and [Tyr³]-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 [Tyr³]-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 [(畏⁶-Cp*Rh-Tyr¹)-leu-enkephalin](OTf)₂ and [(畏⁶-Cp*Rh-Tyr³)-octreotide](OTf)₂.