Polymers

Oxford Nanopore's platform technology has the potential to identify single molecules along a chain passing through the nanopore, as well as individual polymer molecules passing through or near the nanopore. Oxford Nanopore and its collaborators are working to develop methods of polymer analysis using nanopores; publications can be found here.

Polymers are large molecules composed of repeating, chemically-similar structural units.  Frequently linear or branched linear molecules examples of biopolymers are:

 

 

Polynucleotides
  • Nucleic acids (DNA and RNA) in which the basic structural units are nucleotides, linked together via phosphodiester bonds.  Four different types of nucleotide (G, T, A, C) enable a huge diversity in polynucleotide sequence (DNA or RNA), dependent on length of the polymer.  Additional 'modified' bases extend the potential combinations even further.
  • Oxford Nanopore is developing a technology platform for DNA sequencing that will evolve through technology generations. The first generation uses an enzyme to cleave individual bases from the end of a DNA molecule for analysis using a protein nanopore. This process is described elsewhere on the site.
  • Future generations of nanopore sequencing technology analyse single strands of DNA as they pass through a nanopore. Research is underway into this method in our collaborators' laboratories; see publications below.
  • Ultimately, DNA polymers may be sequenced using nanopores fabricated from man-made materials rather than protein - this is referred to as 'solid-state' nanopore sequencing.
  • The modularity of the technology means that the nanopore-enzyme construct could be changed to process RNA instead of DNA.
  • Click here for details of our Technology Advisory Panel, with whom we are working on today and tomorrow's generations of nanopore DNA sequencing.

 

 

Polypeptides
  • A polypeptide is formed by a series of amino acids linked together via peptide bonds. A protein is composed of a series of polypeptides. There are 20 different amino acids, enabling huge diversity of protein primary sequences. Diversity comes through the length of the polymer as well as the combination of amino acids.
  • Some research has been performed into the translocation of polypeptides through a nanopore for identification - please see the publication list below.
  • Nanopores can be used to identify proteins in their 'normal' state rather than as their polypeptide 'unfolded' form.  Click here for more details.  

 

 


Polysaccharides
  • Polysaccharides are composed of a variety of mono- or disaccharides linked by glycosidic bonds. Examples are carbohydrates, such as starch (energy storage) or cellulose (structural). With a huge number of mono- and disaccharides, there is an almost infinite number of distinct heteropolysaccharide species that can be generated.
  • Some research has been performed on the interaction between nanopores and polysaccharides.

 

 


Synthetic polymers
  • A number of synthetic polymers exist, for example plastics or dendrimers. These are commonly, but not exclusively, cross-linked materials, unlike the basic linear structures associated with biopolymers.

 

 

Publications:

 

Polypeptides

 

Interactions of peptides with a protein pore. Biophys. J. 89 (2), 1030-1045 (2005)

 

Polysaccharides

 

Interaction of the noncovalent molecular adapter, beta-cyclodexterin, with the staphylococcal alpha hemolysin pore. Biophys. J. 79 (4), 1967-1975 (2000).

 

Polynucleotides 

 

Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore. PNAS 106 (19), 7702-7707 (2009)
A single-molecule nanopore device detects DNA polymerase activity with single nucleotide resolution. J. Am. Chem. Soc. 103 (3), 818-820 (2008)
Enhanced translocation of single DNA molecules through α-hemolysin nanopores by manipulation of internal charge. PNAS 105 (50), 19720-19725 (2008)
Probing distance and electrical potential within a protein pore with tethered DNA. Biophys. J. 83 (6), 3202-3210 (2002)