Peptidomimetic compounds that inhibit antigen presentation by autoimmune disease-associated class II major histocompatibility molecules.

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 Biotechnol

journal_title

Nature biotechnology

authors

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 ZA

doi

10.1038/9865

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

562-7

issue

6

eissn

1087-0156

issn

1546-1696

journal_volume

17

pub_type

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