umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Design, synthesis and evaluation of N-acyl modified sialic acids as inhibitors of EKC-causing adenoviruses
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
Visa övriga samt affilieringar
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
Identifikatorer
URN: urn:nbn:se:umu:diva-3172OAI: oai:DiVA.org:umu-3172DiVA, id: diva2:141662
Tillgänglig från: 2008-05-08 Skapad: 2008-05-08 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Design and Synthesis of Sialic Acid Conjugates as Inhibitors of EKC-causing Adenoviruses
Öppna denna publikation i ny flik eller fönster >>Design and Synthesis of Sialic Acid Conjugates as Inhibitors of EKC-causing Adenoviruses
2008 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The combat against viral diseases has been, and still is, a major challenge in the field of drug development. Viruses are intracellular parasites that use the host cell ma-chinery for their replication and release. Therefore it is difficult to target and destroy the viral particle without disturbing the essential functions of the host cell. This thesis describes studies towards antiviral agents targeting adenovirus type 37 (Ad37), which causes the severe ocular infection epidemic keratoconjunctivitis (EKC). Cell surface oligosaccharides serve as cellular receptors for many pathogens, including viruses and bacteria. For EKC-causing adenoviruses, cell surface oligo-saccharides with terminal sialic acid have recently been shown to be critical for their attachment to and infection of host cells. The work in this thesis support these re-sults and identifies the minimal binding epitope for viral recognition. As carbo-hydrate–protein interactions in general, the sialic acid–Ad37 interaction is very weak. Nature overcomes this problem and vastly improves the binding affinity by presenting the carbohydrates in a multivalent fashion. Adenoviruses interact with their cellular receptors via multiple fiber proteins, whereby it is likely that the ideal inhibitor of adenoviral infections should be multivalent. This thesis includes design and synthesis of multivalent sialic acid glycoconjugates that mimic the structure of the cellular receptor in order to inhibit adenoviral attachment to and infection of human corneal epithelial (HCE) cells. Synthetic routes to three different classes of sialic acid conjugates, i.e. derivatives of sialic acid, 3’-sialyllactose and N-acyl modified sialic acids, and their multivalent counterparts on human serum albumine (HSA) have been developed. Evaluation of these conjugates in cell binding and cell infectivity assays revealed that they are effective as inhibitors. Moreover the results verify the hypothesis of the multivalency effect and clearly shows that the power of inhibition is significantly increased with higher orders of valency. Potential inhibi-tors could easily be transferred to the eye using a salve or eye drops, and thereby they would escape the metabolic processes of the body, a major drawback of using carbohydrates as drugs. The results herein could therefore be useful in efforts to develop an antiviral drug for treatment of EKC.

Ort, förlag, år, upplaga, sidor
Umeå: Kemi, 2008. s. 84
Nyckelord
Sialic acid, sialylmimetics, sialylation, multivalency, glycoconjugates, adenovirus, antiviral agents, epidemic keratoconjunctivitis
Nationell ämneskategori
Organisk kemi
Identifikatorer
urn:nbn:se:umu:diva-1641 (URN)978-91-7264-545-5 (ISBN)
Disputation
2008-05-30, KB3B1, KBC, KBC-Huset, Umeå Univeristet, Umeå, 10:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2008-05-08 Skapad: 2008-05-08 Senast uppdaterad: 2018-06-09Bibliografiskt granskad

Open Access i DiVA

Fulltext saknas i DiVA

Personposter BETA

Johansson, SusanneNilsson, EmmaQian, WeixingArnberg, NiklasKihlberg, JanElofsson, Mikael

Sök vidare i DiVA

Av författaren/redaktören
Johansson, SusanneNilsson, EmmaQian, WeixingArnberg, NiklasKihlberg, JanElofsson, Mikael
Av organisationen
Kemiska institutionenInstitutionen för klinisk mikrobiologi

Sök vidare utanför DiVA

GoogleGoogle Scholar

urn-nbn

Altmetricpoäng

urn-nbn
Totalt: 144 träffar
RefereraExporteraLänk till posten
Permanent länk

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