Abstract:
:We have identified a heptapeptide with high affinity to rheumatoid arthritis-associated class II major histocompatibility (MHC) molecules. Using a model of its interaction with the class II binding site, a variety of mimetic substitutions were introduced into the peptide. Several unnatural amino acids and dipeptide mimetics were found to be appropriate substituents and could be combined into compounds with binding affinities comparable to that of the original peptide. Compounds were designed that were several hundred-fold to more than a thousand-fold more potent than the original peptide in inhibiting T-cell responses to processed protein antigens presented by the target MHC molecules. Peptidomimetic compounds of this type could find therapeutic use as MHC-selective antagonists of antigen presentation in the treatment of autoimmune diseases.
journal_name
Nat Biotechnoljournal_title
Nature biotechnologyauthors
Falcioni F,Ito K,Vidovic D,Belunis C,Campbell R,Berthel SJ,Bolin DR,Gillespie PB,Huby N,Olson GL,Sarabu R,Guenot J,Madison V,Hammer J,Sinigaglia F,Steinmetz M,Nagy ZAdoi
10.1038/9865subject
Has Abstractpub_date
1999-06-01 00:00:00pages
562-7issue
6eissn
1087-0156issn
1546-1696journal_volume
17pub_type
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