Synthesis,antibody recognition and enzymatic stability of linear,cyclic and branched polypeptides containing a beta-amyloid plaque specific epitope

摘要

Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for possible vaccination to the treatment of Alzheimer's disease(AD).However,a therapeutic trial of immunisation with A beta(1-42)in humans was discontinued due to significant toxic side effects such as meningo-encephalitic cellular inflammatory reactions.Using the epitope excision method in combination with high resolution mass spectrometry,the N-terminal A beta(4-10)(~4FRHDSGY~(10))sequence has been identified as the core epitope region recognized by therapeutically active antibodies raised against A beta(1-42)and/or its oligomeric assemblies.This finding provides the basis for the design of new artificial antigens for specific immunization which are independent of the A beta(1-42)structure,aggregation propensity and toxicity.Here we report on the synthesis and biochemical characterization of several antigens comprising the A beta(4-10)epitope as new lead vaccine structures against Alzheimer's disease.