Synthesis and Evaluation of Phosphopeptides Containing Iminodiacetate Groups as Binding Ligands of the Src SH2 Domain
Phosphopeptide pTyr-Glu-Glu-Ile (pYEEI) has been introduced as an optimal Src SH2 domain ligand. Peptides, Ac-K(IDA)pYEEIEK(IDA) (1), Ac-KpYEEIEK (2), Ac-K(IDA)pYEEIEK (3), and Ac-KpYEEIEK(IDA) (4), containing 0–2 iminodiacetate (IDA) groups at the N- and C-terminal lysine residues were synthesized and evaluated as the Src SH2 domain binding ligands. Fluorescence polarization assays showed that peptide 1 had a higher binding affinity (Kd = 0.6 μM) to the Src SH2 domain when compared with Ac-pYEEI (Kd = 1.7 μM), an optimal Src SH2 domain ligand, and peptides 2–4 (Kd = 2.9–52.7 μM). The binding affinity of peptide 1 to the SH2 domain was reduced by more than 2-fold (Kd = 1.6 μM) upon addition of Ni2+ (300 μM), possibly due to modest structural effect of Ni2+ on the protein as shown by circular dichroism experimental results. The binding affinity of 1 was restored in the presence of EDTA (300 μM) (Kd = 0.79 μM). These studies suggest that peptides containing IDA groups may be used for designing novel SH2 domain binding ligands.
Ye, Guofeng, Aaron D. Schuler, Yousef Ahmadibeni, Joel R. Morgan, Absar Faruqui, Kezhen Huang, Gongqin Sun, John A. Zebala, and Keykavous Parang. "Synthesis and evaluation of phosphopeptides containing iminodiacetate groups as binding ligands of the Src SH2 domain." Bioorganic chemistry 37, no. 4 (2009): 133-142.
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NOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic Chemistry, volume 37, issue 4, in 2009. DOI: 10.1016/j.bioorg.2009.05.003
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