"Click peptides"--chemical biology-oriented synthesis of Alzheimer's disease-related amyloid beta peptide (abeta) analogues based on the "O-acyl isopeptide method".

Abstract

A clear understanding of the pathological mechanism of amyloid beta peptide (Abeta) 1-42, a currently unexplained process, would be of great significance for the discovery of novel drug targets for Alzheimer's disease (AD) therapy. To date, though, the elucidation of these Abeta1-42 dynamic events has been a difficult issue because of uncontrolled polymerization, which also poses a significant obstacle in establishing experimental systems with which to clarify the pathological function of Abeta1-42. We have recently developed chemical biology-oriented pH- or phototriggered "click peptide" isoform precursors of Abeta1-42, based on the "O-acyl isopeptide method", in which a native amide bond at a hydroxyamino acid residue, such as Ser, is isomerized to an ester bond, the target peptide subsequently being generated by an O-N intramolecular acyl migration reaction. These click peptide precursors did not exhibit any self-assembling character under physiological conditions, thanks to the presence of the one single ester bond, and were able to undergo migration to give the target Abeta1-42 in a quick and easy, one-way (so-called "click")conversion reaction. The use of click peptides could be a useful strategy to investigate the biological functions of Abeta1-42 in AD through inducible activation of Abeta1-42 self-assembly.

• Authors: Youhei Sohma, Yoshiaki Kiso
• Journal: Chembiochem : a European journal of chemical biology (Chembiochem) Vol. 7 Issue 10 Pg. 1549-57 (Oct 2006) ISSN: 1439-4227 [Print] Germany
• PMID: 16915597 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Amides
• Amyloid beta-Peptides
• Esters
• Peptide Fragments
• Protein Isoforms
• amyloid beta-protein (1-42)

Topics

• Alzheimer Disease (metabolism, pathology)
• Amides (chemistry)
• Amino Acid Sequence
• Amyloid beta-Peptides (chemical synthesis, chemistry, genetics, metabolism)
• Esters (chemistry)
• Humans
• Hydrogen-Ion Concentration
• Molecular Sequence Data
• Molecular Structure
• Peptide Fragments (chemical synthesis, chemistry, genetics, metabolism)
• Protein Isoforms (chemical synthesis, chemistry, genetics, metabolism)