FISLE-412 is the first reported small molecule peptidomimetic that neutralizes anti-dsDNA autoantibodies associated with systemic lupus erythematosus (SLE) pathogenesis. FISLE-412 is a complex molecule that involves a challenging synthesis scheme, but has attractive pharmacological activities as a potential small molecule therapeutic in lupus. Therefore, we initiated a structure-activity investigation of FISLE-412. We synthesized a small library of mimetopes around FISLE-412 and identified several analogues which could neutralize anti-DNA lupus antibodies <i>in vitro </i>and in <i>vivo</i>. Our strategies managed to reduce the structural complexity of FISLE-412 and provide important information that may guide potential autoantibody-targeted lupus therapeutics.

Structural investigation of FISLE-412, a peptidomimetic compound derived from saquinavir that targets lupus autoantibodies

252nd National Meeting (2016)

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