Polymers (deriving from the Greek, polis: many, meros: part) 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 as 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 may 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' nanopores.
- 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 may 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
Translocation of polypeptides through a protein pore: Movileanu, L., SchmittschmittJ.P., Scholtz, J.M. and Bayley,
H. (2005) Interactions of peptides
with a protein pore. Biophys. J. 89;
1030-1045
Polysaccharides
Detection of cyclic polysaccharides, which are themselves
adapters that can lend discriminatory selectivity to the protein pore: Gu, L.Q. and Bayley, H. (2000) Interaction of the noncovalent
molecular adapter, beta-cyclodexterin, with the staphylococcal alpha hemolysin
pore. Biophys. J. 2000 79;
1967-1975.
Polynucleotides
Analysis of nucleotide identity on an immobilised DNA strand: Stoddart, D., Heron, A.J., Mikhailova, E., Maglia, G. and Bayley,
H. (2009) Single-nucleotide discrimination in immobilized DNA oligonucleotides
with a biological nanopore. PNAS 106;
7702-7707
Transit of nucleic acids and analysis of base identity
through the nanopore:
Cockcroft, S.L., Chu, J., Amorin, M., Bayley, H. and
Ghadiri, M.R. (2008) A
single-molecule nanopore device detects DNA polymerase activity with single
nucleotide resolution. J. Am.
Chem. Soc. 103, 818-820
Maglia, G., Restrepo, M.R., Mikhailova, E. and Bayley, H.
(2008) Enhanced translocation of single DNA molecules through α-hemolysin
nanopores by manipulation of internal charge. PNAS. USA 105; 19720-19725
Capture of specific analyte nucleic acid sequences on a
covalently attached complementary strand:
Horworka, S. and Bayley, H. (2002) Probing distance and
electrical potential within a protein pore with tethered DNA. Biophys. J. 83; 3202-3210
Oxford Nanopore's platform technology has the potential to identify single molecules along a chain passing through the nanopore, as well as individual 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.