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I-Domain-Antigen Conjugate (IDAC) for Delivering Antigenic Peptides to APC: Synthesis, Characterization, and in vivo EAE Suppression
Manikwar, Prakash Büyüktimkin, Barlas Kiptoo, Paul Badawi, Ahmed H. Galeva, Nadezhda A. Williams, Todd D. Siahaan, Teruna J.
Manikwar, Prakash
Büyüktimkin, Barlas
Kiptoo, Paul
Badawi, Ahmed H.
Galeva, Nadezhda A.
Williams, Todd D.
Siahaan, Teruna J.
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Abstract
The objectives of this work are to characterize the identity of I-domain-antigen conjugate (IDAC) and to evaluate the in vivo efficacy of IDAC in suppressing experimental autoimmune encephalomyelitis (EAE) in mouse model. The hypothesis is that the I-domain delivers PLP139-151 peptides to antigen-presenting cells (APC) and alters the immune system by simultaneously binding to ICAM-1 and MHC-II, blocking immunological synapse formation. IDAC was synthesized by derivatizing the lysine residues with maleimide groups followed by conjugation with PLP-Cys-OH peptide. Conjugation with PLP peptide does not alter the secondary structure of the protein as determined by CD. IDAC suppresses the progression of EAE while I-domain and GMB-I-domain could only delay the onset of EAE. As a positive control, Ac-PLP-BPI-NH2-2 can effectively suppress the progress of EAE. The number of conjugation sites and the sites of conjugations in IDAC were determined using tryptic digest followed by LC-MS analysis. In conclusion, conjugation of I-domain with an antigenic peptide (PLP) resulted in an active molecule to suppress EAE in vivo.
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2012-03-21
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ACS
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Manikwar_ACS_2012.pdf
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Manikwar, P., Büyüktimkin, B., Kiptoo, P., Badawi, A. H., Galeva, N. A., Williams, T. D., & Siahaan, T. J. (2012). I-Domain-Antigen Conjugate (IDAC) for Delivering Antigenic Peptides to APC: Synthesis, Characterization, and in vivo EAE Suppression. Bioconjugate Chemistry, 23(3), 509–517. http://doi.org/10.1021/bc200580j