Potential lead for an Alzheimer drug: a peptide that blocks intermolecular interaction and amyloid beta protein-induced cytotoxicity.
A peptide chAbeta30-16 (15-mer; CTFVRTHIFCKEHQF) was designed to bind to a region encompassing the entire polymerization-related (16KLVFF20) and part of the polymerization and toxicity-related (25GSNKGAIIGLM35) regions of amyloid beta-protein, Abeta1-42 by a hydropathic complementary approach. This peptide efficiently binds to Abeta and blocks intermolecular interaction and the formation of Abeta aggregates. In addition, the peptide neutralizes the cell toxicity of Abeta fibrils. The chAbeta30-16 peptide or its derivatives may be a starting point for the future development of drugs that prevent the neurotoxicity and deposition of Abeta in the brain of Alzheimer's disease.
Kwak
Ju-Won
JW
Division of Molecular and Life Sciences, Postech Biotech Center, Pohang University of Science and Technology, San31 Hyoja-dong, Pohang, Kyungbuk 790-784, Republic of Korea.
Kim
Hyun-Kyung
HK
Chae
Chi-Bom
CB
D000544:Alzheimer Disease / Q000188:drug therapy*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D008969:Molecular Sequence Data; D018697:Nootropic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
D016229:Amyloid beta-Peptides; D018697:Nootropic Agents; D010455:Peptides; C513360:chAbeta30-16 peptide