Subject(s)
Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Type 2/complications , Hypertension/complications , Hypertension/drug therapy , Indapamide/therapeutic use , Perindopril/therapeutic use , Drug Combinations , Humans , Randomized Controlled Trials as TopicSubject(s)
Anthracyclines/metabolism , Glycosyltransferases/biosynthesis , Glycosyltransferases/genetics , Protease Inhibitors , Anthracyclines/pharmacology , Cell Line , Cell Proliferation/drug effects , Cloning, Molecular , DNA, Bacterial/genetics , Molecular Sequence Data , Multigene Family , Plasmids/genetics , Protease Inhibitors/pharmacology , Streptomyces/enzymology , Streptomyces/geneticsABSTRACT
A mirror image phage display approach was used to identify novel and highly specific ligands for Alzheimer's disease amyloid peptide Abeta(1-42). A randomized 12-mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of Abeta(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 Abeta(1-42) with a dissociation constant in the submicromolar range. Furthermore, in brain tissue sections derived from patients that suffered from Alzheimer's disease, amyloid plaques and leptomeningeal vessels containing Abeta amyloid were stained specifically with a fluorescence-labeled derivative of D-pep. Fibrillar deposits derived from other amyloidosis were not labeled by D-pep. Possible applications of this novel and highly specific Abeta ligand in diagnosis and therapy of Alzheimer's disease are discussed.
Subject(s)
Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Brain/metabolism , Peptide Fragments/metabolism , Peptide Library , Plaque, Amyloid/metabolism , Amino Acid Sequence , Amyloid beta-Peptides/chemistry , Amyloid beta-Peptides/genetics , Amyloidosis/metabolism , Humans , Ligands , Molecular Sequence Data , Peptide Fragments/chemistry , Peptide Fragments/genetics , Plaque, Amyloid/genetics , Protein Binding/physiologyABSTRACT
Three fused octacyclic phenylphenalenone dimers were isolated from Musa acuminata: Anigorootin, which was first isolated from Anigozanthos flavidus and hitherto represented the only compound of that type, the new 4'-hydroxy-anigorootin, and 4',4"-di-hydroxy-anigorootin, which is a revised structure. The crystal structure of anigorootin was determined by X-ray crystallography. 3,3'-Bis-hydroxyanigorufone, a dimer of the conventional type known from Anigozanthos preissii, was also found in Musa acuminata. Phytochemical analysis of several Haemodoraceae species revealed the occurrence of anigorootin, 3,3'-bis-hydroxyanigorufone, and the novel metabolite 3,3'-bis-anigorufone. The occurrence of the same compounds in Musaceae and Haemodoraceae indicates the close chemotaxonomic relationship of both plant families.
