umu.sePublikasjoner
Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
A Generic Method for Design of Oligomer-Specific Antibodies
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
Vise andre og tillknytning
2014 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, s. e90857-Artikkel i tidsskrift (Fagfellevurdert) 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.

sted, utgiver, år, opplag, sider
2014. Vol. 9, nr 3, s. e90857-
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-88327DOI: 10.1371/journal.pone.0090857ISI: 000332842400033OAI: oai:DiVA.org:umu-88327DiVA, id: diva2:725505
Tilgjengelig fra: 2014-06-16 Laget: 2014-04-30 Sist oppdatert: 2018-06-07bibliografisk kontrollert

Open Access i DiVA

fulltext(7569 kB)325 nedlastinger
Filinformasjon
Fil FULLTEXT01.pdfFilstørrelse 7569 kBChecksum SHA-512
d72c104aa2e8f12bdc0e8a156545a9bfcf706894c82e6d69d61f44ce9b522c5b75838076d22ab571f23b2a1669ff98d54139304b40a9259429c7a80981f6fe01
Type fulltextMimetype application/pdf

Andre lenker

Forlagets fulltekst

Personposter BETA

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

Søk i DiVA

Av forfatter/redaktør
Brännström, KristofferLindhagen-Persson, MalinGharibyan, Anna L.Iakovleva, IrinaSellin, Mikael E.Brännström, ThomasMorozova-Roche, LudmillaForsgren, LarsOlofsson, Anders
Av organisasjonen
I samme tidsskrift
PLoS ONE

Søk utenfor DiVA

GoogleGoogle Scholar
Totalt: 325 nedlastinger
Antall nedlastinger er summen av alle nedlastinger av alle fulltekster. Det kan for eksempel være tidligere versjoner som er ikke lenger tilgjengelige

doi
urn-nbn

Altmetric

doi
urn-nbn
Totalt: 721 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf