II. La chimie des modèles

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1 II. La chimie des modèles

2 Biomimétisme vs. bioinspirée

3 Biomimétisme vs. bioinspirée

4 IIa. La chimie de la vie

5 « We not only want to know how Nature is (and how her transactions are carried through), but we also want to reach, if possible, a goal which may seem utopian and presumptuous, namely, to know why Nature is such and not otherwise. » Albert Einstein in Festschrift für Aurel Stodola, E. Honegger, Ed. (Orell Füssli, Zürich, 1929).

6 La structure en double hélice de l’ADN violerait-elle les lois élémentaires de la chimie?
« … duplex structure appears to violate many of the rules that chemists might themselves use to design molecular recognition systems. For example, the double helix appears to disregard Coulomb’s law. Cations bind anions, and anion bind cations. In DNA, however, a polyanion binds another polyanion. One might think (and indeed, many have thought) that the duplex would be more stable if one strand were uncharged, or polycationic. Likewise, chemists often exploit rigidity when designing receptors to fit ligands. DNA strands are floppy. One would think (and many have thought) that conformationally rigid DNA analogues should be better at molecular recognition. Another curious feature of the DNA duplex is its use of hydrogen bonding to achieve specificity. This would not be the chemist’s preference in water, where hydrogen bonding to solvent competes with interstrand hydrogen bonding. Indeed, several groups have sought to dispense with hydrogen bonding between nucleobases entirely. » Steven A. Benner Acc. Chem. Res. 2004, 37, 784

7 ADN, 3 éléments indispensables?
3’ 5’ T C G A

8 Peut-on changer les bases nucléïques?

9 Cinq nouveaux appariements possibles

10 Pyrimidine > pyridine ~ pyrazine

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13 5’--CACN1ACTTTCTCCT-3’ 3’-TGTGN2TGAAAGAGG--5’
Vers un alphabet génétique artificiel Artificially Expanded Genetic Information System (AEGIS) 5’--CACN1ACTTTCTCCT-3’ 3’-TGTGN2TGAAAGAGG--5’

14 Pu-py appariements 3 2 1

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16 Py-py appariements 3 2 1 5O°C

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18 Pu-pu appariements 2 5O°C

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20 Peut-on changer les bases nucléïques?
Réponse : oui du point de vue de la chimie Du point de vue de la biologie, la question est de savoir si la Nature acceptera de nouvelles nucléobases. « Ligases, kinases, and other workhorses of molecular biology accept AEGIS components. So does the ribosome. In a collaboration with James Bain and Richard Chamberlin at the University of California at Irvine, we challenged the ribosome from Escherichia coli to translate a mRNA containing a 65th codon built using AEGIS components and synthesize a protein with a 21st amino acid. When given a charged tRNA carrying the anticodon incorporating the appropriate AEGIS complement, a nonstandard peptide was synthesized. This study also showed how release factors work in natural systems to terminate translation. Steven A. Benner Acc. Chem. Res. 2004, 37, à paraître Le problème à résoudre est la polymérase

21 A four-base paired genetic helix with expanded size H. Liu, J. Ga, S. R. Lynch, D. Saito, L. Maynard and E. T. Kool Science 2003, 302, 10.7 Å 12.9 Å

22 Stabilité du duplex d(xATxAxATxATTxAT) d(AxTAAxTAxTxTAxT)
d(xAxTxAxAxTxAxTxTxAxT) Contrôle : d(ATAATATTAT)

23 Artificial metallo-DNA: a bio-inspired approach to metal array programming M. Shionoya and K. Tanaka Current Opinion in Chemical Biology 2004, sous presse.

24 Augmentation de la diversité

25 Augmentation de la diversité…

26 Vers de futur matériaux

27 La structure en hélice est respectée…

28 Peut-on changer les liens phosphate?
Sulfone-linked RNAs permettent des appariements de type Watson-Crick pour des courtes séquences mais pas avec de longues séquences (agrégation). La répétition de charge sur le squelette de l’ADN semble être de nature universelle.

29 Peut-on changer le ribose?
1’,2’-seco-ADN homo-ADN Structure des oligonucléotides complètement différentes Reconnu par DNA et RNA pol.

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31 Chimie pré-biotique