Document Type
Article
Date of Original Version
2009
Abstract
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.
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Citation/Publisher Attribution
Ye, G., Schuler, A. D., Ahmadibeni, Y., Morgan, J. R., Faruqui, A., Huang, K., Sun, G.,...Parang, K. (2009). Synthesis and evaluation of phosphopeptides containing iminodiacetate groups as binding ligands of the Src SH2 domain. Bioorganic Chemistry, 37(4), 133-142. doi: 10.1016/j.bioorg.2009.05.003
Available at: https://doi.org/10.1016/j.bioorg.2009.05.003
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comment
Guofeng Ye, Yousef Ahmadibeni and Keykavous Parang are from the Department of Biomedical and Pharmaceutical Sciences.
Kezhen Huang and Gongqin Sun are from the Department of Cell and Molecular Biology.
Author Manuscript
This is a pre-publication author manuscript of the final, published article.