Next Article in Journal
Anti-Inflammatory Effect of IL-37-Producing T-Cell Population in DSS-Induced Chronic Inflammatory Bowel Disease in Mice
Previous Article in Journal
The Aryl Hydrocarbon Receptor and the Maintenance of Lung Health
Article Menu
Issue 12 (December) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(12), 3883; https://doi.org/10.3390/ijms19123883

2′-Fluoro-Pyrimidine-Modified RNA Aptamers Specific for Lipopolysaccharide Binding Protein (LBP)

1
Jasmin Aldag, EUROIMMUN AG, Seekamp 31, D-23560 Lübeck, Germany
2
Tina Persson, Passage2Pro AB, Östra Kristinelundsvägen 4B, SE-21748 Malmö, Sweden
3
Roland K. Hartmann, Philipps-Universität Marburg, Institut für Pharmazeutische Chemie, Marbacher Weg 6, D-35037 Marburg, Germany
*
Author to whom correspondence should be addressed.
Received: 24 October 2018 / Revised: 28 November 2018 / Accepted: 29 November 2018 / Published: 5 December 2018
(This article belongs to the Section Biochemistry)
Full-Text   |   PDF [2784 KB, uploaded 10 December 2018]   |  

Abstract

Lipopolysaccaride binding protein (LBP), a glycosylated acute phase protein, plays an important role in the pathophysiology of sepsis. LBP binds with high affinity to the lipid part of bacterial lipopolysaccaride (LPS). Inhibition of the LPS-LBP interaction or blockage of LBP-mediated transfer of LPS monomers to CD14 may be therapeutical strategies to prevent septic shock. LBP is also of interest as a biomarker to identify septic patients at high risk for death, as LBP levels are elevated during early stages of severe sepsis. As a first step toward such potential applications, we isolated aptamers specific for murine LBP (mLBP) by in vitro selection from a library containing a 60-nucleotide randomized region. Modified RNA pools were transcribed in the presence of 2′-fluoro-modified pyrimidine nucleotides to stabilize transcripts against nuclease degradation. As verified for one aptamer experimentally, the selected aptamers adopt a “three-helix junction” architecture, presenting single-stranded 7-nt (5′-YGCTTCY) or 6-nt (5′-RTTTCY) consensus sequences in their core. The best binder (aptamer A011; Kd of 270 nM for binding to mLBP), characterized in more detail by structure probing and boundary analysis, was demonstrated to bind with high specificity to murine LBP. View Full-Text
Keywords: in vitro selection; aptamer; 2′-fluor-pyrimidine-modified; lipopolysaccaride binding protein (LBP); sepsis; systemic inflammatory response syndrome (SIRS) in vitro selection; aptamer; 2′-fluor-pyrimidine-modified; lipopolysaccaride binding protein (LBP); sepsis; systemic inflammatory response syndrome (SIRS)
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Aldag, J.; Persson, T.; Hartmann, R.K. 2′-Fluoro-Pyrimidine-Modified RNA Aptamers Specific for Lipopolysaccharide Binding Protein (LBP). Int. J. Mol. Sci. 2018, 19, 3883.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top