uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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
Conformational Analysis of Rifampicin in Solution
Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
2018 (English)Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

Rifampicin is a macrocyclic drug used to treat bacterial infections.1 With a mass of 823 Da, rifampicin violates the Lipinki’s rule of five (Ro5),2 and therefore would be expected to have poor membrane permeability, and hence to not be applicable as an oral therapeutic agent. Despite this fact, rifampicin has proven to reach its target in a biological system and thus is able to pass multiple cell membranes without major problems. We hypothesize that the permeability of rifampicin may be explained by its molecular flexibility. We have therefore determined the conformational ensembles of rifampicin in aqueous and in chloroform solutions using the NMR Analysis of Molecular Flexibility in Solution (NAMFIS) approach.3 Comparing the ensembles present in environments possessing different polarities, we hypothesized that simultaneous aqueous solubility and membrane permeability of rifampicin may be explained by its ability to adjust its conformation to the molecular environment. In this presentation the ensemble analysis of rifampicin in polar and non-polar media will be disclosed, and the results will be discussed in relation to the above hypothesis on its permeability. We propose that this macrocycle folds into a conformation with its hydrophilic groups being better shielded from the hydrophobic membrane when it crosses a membrane, whereas it makes its polar functions solvent accessible in a polar environment (Fig. 1).

Place, publisher, year, edition, pages
2018.
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-355761OAI: oai:DiVA.org:uu-355761DiVA, id: diva2:1230741
Conference
Swedish Chemical Society
Available from: 2018-07-04 Created: 2018-07-04 Last updated: 2018-07-04

Open Access in DiVA

No full text in DiVA

By organisation
Department of Chemistry - BMC
Chemical Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • 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