Mechanistic studies of affinity modulation

M. K. Rosen, C. D. Amos, T. J. Wandless

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A synthetic ligand for the protein FKBP12 was covalently linked to a peptide ligand (pYEEI) for the Fyn SH2 protein to create a bifunctional molecule called SLFpYEEI. This bifunctional molecule can simultaneously bind both proteins to form a trimeric complex. When SLFpYEEI is precomplexed with FKBP12, the peptide ligand binds 6-fold more weakly to the Fyn SH2 domain than SLFpYEEI alone. Isotope-edited NMR spectroscopy was used to investigate the molecular basis for the observed reduction in affinity. The results suggest that interactions between the pYEEI peptide and FKBP12 may play a significant role in diminishing the affinity of SLFpYEEI for the Fyn SH2 domain.

Original languageEnglish (US)
Pages (from-to)11979-11982
Number of pages4
JournalJournal of the American Chemical Society
Volume122
Issue number48
DOIs
StatePublished - Dec 6 2000

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Tacrolimus Binding Protein 1A
Peptides
src Homology Domains
Ligands
Modulation
Proteins
Molecules
Isotopes
Nuclear magnetic resonance spectroscopy
Magnetic Resonance Spectroscopy
phosphotyrosyl-glutamyl-glutamyl-isoleucine

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Mechanistic studies of affinity modulation. / Rosen, M. K.; Amos, C. D.; Wandless, T. J.

In: Journal of the American Chemical Society, Vol. 122, No. 48, 06.12.2000, p. 11979-11982.

Research output: Contribution to journalArticle

Rosen, M. K. ; Amos, C. D. ; Wandless, T. J. / Mechanistic studies of affinity modulation. In: Journal of the American Chemical Society. 2000 ; Vol. 122, No. 48. pp. 11979-11982.
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