Design of metastable β-sheet oligomers from natively unstructured peptide

Marcos J. Guerrero-Muñoz, Diana L. Castillo-Carranza, Urmi Sengupta, Mark White, Rakez Kayed

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Amyloid oligomers represent the primary pathological species for neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Toxic oligomers are formed by many different proteins and peptides, but their polydispersity makes them highly dynamic and heterogeneous. One way to stabilize these structures is to prepare constrained peptides that can be used to study amyloid intermediates, to identify oligomer-specific drugs, and to generate conformational antibodies. These conformational antibodies have demonstrated that oligomers share a common epitope. In this research, we used a 40-amino acid unstructured segment of prion protein (Prp) 109-148 with substitutions of methionine for glycine (Prp-G) residues to prepare a stable and homogeneous population of β-sheet oligomer mimics. These structures were characterized by multiple biophysical and biochemical techniques that show characteristic features of oligomers. Finally, this preparation was not detected by three different sequence dependent prion antibodies.

Original languageEnglish (US)
Pages (from-to)1520-1523
Number of pages4
JournalACS Chemical Neuroscience
Volume4
Issue number12
DOIs
StatePublished - Dec 18 2013

Fingerprint

Oligomers
Amyloid
Peptides
Antibodies
Prions
Poisons
Population Dynamics
Neurodegenerative Diseases
Methionine
Glycine
Parkinson Disease
Epitopes
Alzheimer Disease
Neurodegenerative diseases
Amino Acids
Polydispersity
Research
Pharmaceutical Preparations
Proteins
Substitution reactions

Keywords

  • Amyloid oligomer
  • constrained peptide
  • prion

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience

Cite this

Design of metastable β-sheet oligomers from natively unstructured peptide. / Guerrero-Muñoz, Marcos J.; Castillo-Carranza, Diana L.; Sengupta, Urmi; White, Mark; Kayed, Rakez.

In: ACS Chemical Neuroscience, Vol. 4, No. 12, 18.12.2013, p. 1520-1523.

Research output: Contribution to journalArticle

Guerrero-Muñoz, Marcos J. ; Castillo-Carranza, Diana L. ; Sengupta, Urmi ; White, Mark ; Kayed, Rakez. / Design of metastable β-sheet oligomers from natively unstructured peptide. In: ACS Chemical Neuroscience. 2013 ; Vol. 4, No. 12. pp. 1520-1523.
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