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
Amino acid building blocks for Fmoc solid-phase synthesis of peptides phosphocholinated at serine, threonine, and tyrosine
Department of Chemical Biology, Max Planck Institute for Molecular Physiology.
2013 (engelsk)Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 78, nr 6, s. 2715-2719Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Phosphocholination of eukaryotic host cell proteins has recently been identified as a novel post-translational modification important for bacterial pathogenesis. Here, we describe the first straightforward synthetic strategy for peptides containing phosphocholinated serine, threonine, or tyrosine residues using preformed functional amino acid building blocks, fully compatible with standard Fmoc solid-phase peptide synthesis.

sted, utgiver, år, opplag, sider
2013. Vol. 78, nr 6, s. 2715-2719
Emneord [en]
enzymes, nucleotides, phosphocholination, protein modifications
HSV kategori
Forskningsprogram
bioorganisk kemi
Identifikatorer
URN: urn:nbn:se:umu:diva-114327DOI: 10.1021/jo302587gISI: 000316375300057PubMedID: 23373758OAI: oai:DiVA.org:umu-114327DiVA, id: diva2:895048
Tilgjengelig fra: 2016-01-18 Laget: 2016-01-18 Sist oppdatert: 2018-06-07bibliografisk kontrollert
Inngår i avhandling
1. Synthesis and investigation of bacterial effector molecules
Åpne denne publikasjonen i ny fane eller vindu >>Synthesis and investigation of bacterial effector molecules
2016 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

During infections, bacterial microorganisms initiate profound interactions with mammalian host cells. Usually defense mechanisms of the host destroy intruding bacteria in rapid manner. However, many bacterial pathogens have evolved in a way to avoid these mechanisms. By use of effector molecules, which can be small organic molecules or proteins with enzymatic activity, the host is manipulated on a molecular level. Effectors mediating post-translational modifications (PTMs) are employed by many pathogens to influence the biological activity of host proteins. In the presented thesis, two related PTMs are investigated in detail: Adenylylation, the covalent transfer of an adenosine monophosphate group from adenosine triphosphate onto proteins, and phosphocholination, the covalent transfer of a phosphocholine moiety onto proteins. Over the past years, enzymes mediating these modifications have been discovered in several pathogens, especially as a mechanism to influence the signaling of eukaryotic cells by adenylylating or phosphocholinating small GTPases. However, the development of reliable methods for the isolation and identification of adenylylated and phosphocholinated proteins remains a vehement challenge in this field of research. This thesis presents general procedures for the synthesis of peptides carrying adenylylated or phosphocholinated tyrosine, threonine and serine residues. From the resulting peptides, mono-selective polyclonal antibodies against adenylylated tyrosine and threonine have been raised. The antibodies were used as tools for proteomic research to isolate unknown substrates of adenylyl transferases from eukaryotic cells. Mass spectrometric fragmentation techniques have been investigated to ease the identification of adenylylated proteins. Furthermore, this work presents a new strategy to identify adenylylated proteins. Additionally, small effector molecules are involved in the regulation of infection mechanisms. In this work, the small molecule LAI-1 (Legionella autoinducer 1) from the pathogen Legionella pneumophila, the causative agent of the Legionnaire’s disease, was synthesised together with its amino-derivatives. LAI-1 showed are a clear pharmacological effect on the regulation of the life cycle of L. pneumophila, initiating transmissive traits like motility and virulence. Furthermore, LAI-1 was shown to have an effect on eukaryotic cells as well. Directed motility of the eukaryotic cells was significantly reduced and the cytoskeletal architecture was reorganised, probably by interfering with the small GTPase Cdc42.

sted, utgiver, år, opplag, sider
Umeå: Umeå University, 2016. s. 110
Emneord
bacterial effectors, organic synthesis, Legionella, PTM, peptide synthesis, nucleotide chemistry
HSV kategori
Forskningsprogram
bioorganisk kemi
Identifikatorer
urn:nbn:se:umu:diva-114698 (URN)978-91-7601-411-0 (ISBN)
Disputas
2016-02-19, KB3A9, KBC-huset, Umeå University, Umeå, 10:00 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2016-01-29 Laget: 2016-01-26 Sist oppdatert: 2018-06-07bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekstPubMed

Personposter BETA

Albers, Michael F

Søk i DiVA

Av forfatter/redaktør
Albers, Michael F
I samme tidsskrift
Journal of Organic Chemistry

Søk utenfor DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric

doi
pubmed
urn-nbn
Totalt: 155 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