Selection of D-amino-acid peptides that bind to Alzheimer's disease amyloid peptide Ab1-42 by mirror image phage display.

A mirror image phage display approach was used to identify novel and highly specific ligands for Alzheimer's disease amyloid peptide Ab(1-42). A randomized 12-mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of Ab(1-42). After four rounds of selection and amplification the peptides were enriched with a dominating consensus sequence. The mirror image of the most representative peptide (D-pep) was shown to bind Ab(1-42) with a dissocn. const. in the submicromolar range. Furthermore, in brain tissue sections derived from patients that suffered from Alzheimer's disease, amyloid plaques and leptomeningeal vessels contg. Ab amyloid were stained specifically with a fluorescence-labeled deriv. of D-pep. Fibrillar deposits derived from other amyloidosis were not labeled by D-pep. Possible applications of this novel and highly specific Ab ligand in diagnosis and therapy of Alzheimer's disease are discussed.