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Title
Loesliche cyclische Analoga
Date Issued
2005
Author(s)
Patent No
2001-10101430
Abstract
Die Erfindung betrifft ein Peptid mit der biologischen Aktivitaet eines Inhibitors der Amyloidbildung sowie dessen diagnostische und medizinische Verwendungszwecke.
WO 200255552 A UPAB: 20020924 NOVELTY - Peptides (I) that modulate amyloidogenesis comprise beta -amyloid peptide (bAP) with at least one intramolecular bridge, are new. DETAILED DESCRIPTION - INDEPENDENT CLAIMS are also included for the following: (1) antibodies (II) specific for (I); (2) qualitative and/or quantitiative detection (M1) of amyloidogenic bAP or its aggregates using (I) or (II) as probe; and (3) modifying, especially inhibiting, (M2) aggregation of amyloidogenic bAP in a liquid by treatment with (I). ACTIVITY - Nootropic; Neuroprotective. MECHANISM OF ACTION - The intramolecular bridge prevents conversion from the alpha -helical to beta -sheet form, and, by binding to native bAP, prevents this from associating with additional molecules of native peptide. A solution containing 450 micro M each of bAP1-28 and bAP1-28 cyclized between Lys17 and Asp21 was incubated in 10 mM phosphate buffer containing 150 mM sodium chloride and 30% acetonitrile (pH 5.5). Circular dichroism spectra indicated no change in conformation after more than 1 month, but for a solution containing only bAP1-28 conversion to the beta -sheet form was detectable after 10 hour, and subsequently insoluble amyloid was precipitated. USE - (I) and/or antibodies (II) are useful for: (a) preventing and/or treating diseases associated with amyloid formation, specifically Alzheimer's disease; (b) diagnostic detection of bAP or its aggregates; and (c) preparative enrichment, especially removal, of amyloid from liquids, especially body fluids. (I) is also used to raise (II) for diagnosis (including monitoring), therapeutic or research applications, e.g. development of diagnostic/therapeutic agents, and vaccines. ADVANTAGE - (I) are easily prepared in pure form by chemical synthesis, have high biological (especially proteolytic) stability, good solubility, low toxicity with few side effects, and are not significantly immunogenic.
Language
de
Patenprio
DE 2001-10101430 A: 20010113