Lecture 9 Designed self-assembly

with Biomolecules

DNA

Parameters of A-, B-, and Z-DNA Double Helices (after Dickerson, et al., 1982)

Property A-Form B-Form Z-FormHelical sense Right-handed Right-handed Left-handedRepeating helix unit 1 base pair 1 base pair 2 base pairsRotation/base pair (degrees) 33.6 35.9 +/- 4.2 -60/2Mean base pairs/turn 10.7 10.0 +/- 1.2 12Inclination of base normals to helix axis (degrees) +19 -1.2 +/- 4.1 -9Rise/base pair along helix axis (Å) 2.3 3.32 +/- 0.19 3.8Pitch/turn of helix (Å) 24.6 33.2 45.6Mean propeller twist (degrees) +18 +16 +/- 7 ~0

Occurrence Dehydrated Most common Rare - certainin solution sequences

http://www.clunet.edu/BioDev/omm/dna.htm

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Different DNA structures

Copying DNA - the polymerase chain reaction

Copying DNA - the polymerase chain reaction

Copying DNA - the polymerase chain reaction

Attaching things to DNA

1. Biotin Streptavidin interaction - generic molecular adapters2. Thiols - Nanoparticles3. Fluorohores - for sensitive detection4. Proteins - protein/DNA recognition5. Proteins - semi-synthetic conjugation6. Metal - metallisation for conductors

DNA detection using nanoparticle assembly

Chad Mirkin Thiol terminated ssDNA

Sensitivity - femtomol(ar)Selectivity - 100,000 : 1 for point mutations (single base pair changes)

Chad Mirkin

DNA detection using nanoparticle assembly

Chad Mirkin

Using DNA bar codes to detect proteins

Science 2003, 301, 1884-1886.

Chad Mirkin

Using DNA bar codes to detect proteins

Science 2003, 301, 1884-1886.

3 aM

30 aM

Sensitivity

aM = attomolar = 10-18M

Niemeyer DNA protein conjugates - ImmunoPCR

Protein diagnostics using DNA

DNA as a scaffold for something else

Biotin Streptavidin interaction - generic molecular adapters

Niemeyer DNA directed immobilisation (DDI)

DNA as a scaffold for something else

Niemeyer

Protein directed DNA organisation

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Chains Rings Networks

Ionic strength dependent supercoiling

Chembiochem. (2001) 2, p260-4

DNA directed Protein organisation

Niemeyer Enzyme localisationChemBioChem (2003) 2, p242-245

DNA metallisation

Braun, and others Nature (1998) 391, p775-8

DNA metallisation - use of protein masks

Braun, and others Science, (2003) 302, p1380-1382

DNA superstructure metallisation

Finkelstein and others

Yan et al Science (2003) 301 p1882

Ribbons

Finkelstein and others

Yan et al Science (2003) 301 p1882

DNA superstructure metallisation

Grids

DNA superstructures for positioning proteins.

Finkelstein and others

Yan et al Science (2003) 301 p1882

Streptavidin locations determined by Biotin labelled DNA grids

Peptide nanotubes - a silver cloud with a peptide lining

Reches and Gazit Science (2003) 300, p625