Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A Generic Method for Design of Oligomer-Specific Antibodies
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.ORCID iD: 0000-0002-9500-5917
Show others and affiliations
2014 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 3, p. e90857-Article in journal (Refereed) Published
Abstract [en]

Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e. g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the A beta peptide and alpha-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies.

Place, publisher, year, edition, pages
2014. Vol. 9, no 3, p. e90857-
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-88327DOI: 10.1371/journal.pone.0090857ISI: 000332842400033Scopus ID: 2-s2.0-84897516039OAI: oai:DiVA.org:umu-88327DiVA, id: diva2:725505
Available from: 2014-06-16 Created: 2014-04-30 Last updated: 2023-03-24Bibliographically approved

Open Access in DiVA

fulltext(7569 kB)532 downloads
File information
File name FULLTEXT01.pdfFile size 7569 kBChecksum SHA-512
d72c104aa2e8f12bdc0e8a156545a9bfcf706894c82e6d69d61f44ce9b522c5b75838076d22ab571f23b2a1669ff98d54139304b40a9259429c7a80981f6fe01
Type fulltextMimetype application/pdf

Other links

Publisher's full textScopus

Authority records

Brännström, KristofferLindhagen-Persson, MalinGharibyan, Anna L.Iakovleva, IrinaSellin, Mikael E.Brännström, ThomasMorozova-Roche, LudmillaForsgren, LarsOlofsson, Anders

Search in DiVA

By author/editor
Brännström, KristofferLindhagen-Persson, MalinGharibyan, Anna L.Iakovleva, IrinaSellin, Mikael E.Brännström, ThomasMorozova-Roche, LudmillaForsgren, LarsOlofsson, Anders
By organisation
Department of Medical Biochemistry and BiophysicsDepartment of Molecular Biology (Faculty of Medicine)PathologyClinical Neuroscience
In the same journal
PLOS ONE
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar
Total: 532 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 1007 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf