Controlled production of amyloid beta peptide from a photo-triggered, water-soluble precursor "click peptide".
In biological experiments, poor solubility and uncontrolled assembly of amyloid beta peptide (Abeta) 1-42 pose significant obstacles to establish an experiment system that clarifies the function of Abeta1-42 in Alzheimer's disease (AD). Herein, as an experimental tool to overcome these problems, we developed a water-soluble photo-"click peptide" with a coumarin-derived photocleavable protective group that is based on an O-acyl isopeptide method. The click peptide had nearly 100-fold higher water solubility than Abeta1-42 and did not self-assemble, as the isomerized structure in its peptide backbone drastically changed the conformation that was derived from Abeta1-42. Moreover, the click peptide afforded Abeta1-42 quickly under physiological conditions (pH 7.4, 37 degrees C) by photoirradiation followed by an O-N intramolecular acyl migration. Because the in situ production of intact Abeta1-42 from the click peptide could improve the difficulties in handling Abeta1-42 caused by its poor solubility and highly aggregative nature, this click peptide strategy would provide a reliable experiment system for investigating the pathological function of Abeta1-42 in AD.
Taniguchi
Atsuhiko
A
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Kyoto, Japan.
Skwarczynski
Mariusz
M
Sohma
Youhei
Y
Okada
Takuma
T
Ikeda
Keisuke
K
Prakash
Halan
H
Mukai
Hidehito
H
Hayashi
Yoshio
Y
Kimura
Tooru
T
Hirota
Shun
S
Matsuzaki
Katsumi
K
Kiso
Yoshiaki
Y
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry; D002942:Circular Dichroism; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects*; D010777:Photochemistry; D011487:Protein Conformation / Q000528:radiation effects; D012995:Solubility
D016229:Amyloid beta-Peptides; D010455:Peptides