DNA Metalcomplex

8/14/2019 DNA Metalcomplex

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Recollection of well knownRecollection of well knowntheories, chemistry andtheories, chemistry and

biologybiology

DNA detective

Rajalakshmi


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DNA isDNA is too smalltoo small to see, but under ato see, but under amicroscope it looks like a twisted upmicroscope it looks like a twisted upladder!ladder!

DNA stands for:D: DeoxyriboseN: NucleicA: Acid

RNA stands for:R: RiboseN: NucleicA: Acid


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Nucleic acidsNucleic acids

In most livingorganisms(except forviruses), genetic information is storedin themoleculedeoxyribonucleicacid,orDNA. DNA is made and resides inthenucleusof living cells. DNA gets itsname from the sugar moleculecontained in its

backbone(deoxyribose);

36 base pairs

Backbone - blue;Bases- gray
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Major bases in nucleic acidsMajor bases in nucleic acids

Among the pyrimidines, C

occurs in both RNA andDNA, but T occurs in DNA, and U occurs in RNA

The bases are

abbreviated by their firstletters (A, G, C, T, U).

The purines (A, G) occurin both RNA and DNA


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Structure of nucleosidesStructure of nucleosides

Remove the phosphate group, and you have a nucleoside.

H


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Structure of nucleotidesStructure of nucleotides

A phosphate group

Nucleotides have three characteristic components:

A nitrogenous base(pyrimidines or purine)

A pentose sugar


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Chemical compositionChemical composition

DNA is a polymer of nucleotides. NucleotidesDNA is a polymer of nucleotides. Nucleotidesconsist of:consist of:

deoxyribose (5-carbon) sugardeoxyribose (5-carbon) sugar

nitrogenous basenitrogenous basephosphate group(s)phosphate group(s)

There are four nitrogenous bases used to make the fourThere are four nitrogenous bases used to make the fourtypes of nucleotides found in a DNA molecule:types of nucleotides found in a DNA molecule:

Adenine, Thymine, Cytosine and Guanine.Adenine, Thymine, Cytosine and Guanine.


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Nucleotides and nucleic acidsNucleotides and nucleic acids

Nucleotides are the building blocks of nucleic acids

NucleotideDNARNA


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Base + sugar = NucleosideBase + sugar = Nucleoside

Base + sugar + phosphate = NucleotideBase + sugar + phosphate = Nucleotide

Nucleotides are stronger because of theNucleotides are stronger because of the

phosphate linkagephosphate linkage

Sugar is Ribose its RNA whereas if it isSugar is Ribose its RNA whereas if it is

Deoxy ribose then DNADeoxy ribose then DNA


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Interstrand H-bonding between DNA basesInterstrand H-bonding between DNA bases

Watson-Crick base pairing


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Pyrimidine and purinePyrimidine and purine

Nucleotide bases in nucleic acids are pyrimidines or purines.


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DeoxyribonucleotidesDeoxyribonucleotides

2'-deoxyribose sugar

Deoxyribonucleotides are abbreviated (for example) A, or

dA (deoxyA).

Phosphorylate the 5' position

and a nucleotide(here,deoxyadenylate ordeoxyguanylate)

with a base (here, a purine,adenine or guanine)

attached to the C-1'position is adeoxyribonucleoside(here deoxyadenosine anddeoxyguanosine).


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There are four nitrogenous bases that areThere are four nitrogenous bases that arefound in DNA: adenine, thymine, guaninefound in DNA: adenine, thymine, guanineand cytosine.and cytosine.

Adenine and thymine areAdenine and thymine are purinepurine bases (2-bases (2-ring structure)ring structure)

Cytosine and guanine areCytosine and guanine are pyrimidinespyrimidines(single-ring structure)(single-ring structure)
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=pyrimidines&rid=stryer.figgrp.628http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=pyrimidines&rid=stryer.figgrp.628http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=pyrimidines&rid=stryer.figgrp.628http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=pyrimidines&rid=stryer.figgrp.628http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=pyrimidines&rid=stryer.figgrp.628http://www.ncbi.nlm.nih.gov/books/bv.fcgi?highlight=pyrimidines&rid=stryer.figgrp.628


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Backbone of DNA isBackbone of DNA is

The phosphodiester bond of the nucleotideThe phosphodiester bond of the nucleotidechain is formed between the phosphatechain is formed between the phosphateattached to the 5 carbon of one sugar andattached to the 5 carbon of one sugar andthe 3 carbon of the next.the 3 carbon of the next.

The 5 end of the strand bears a phosphateThe 5 end of the strand bears a phosphategroup; the 3 end bears a hydroxyl (OH)group; the 3 end bears a hydroxyl (OH)group.group.

The two strands of DNA in a helical moleculeThe two strands of DNA in a helical moleculeare antiparallel to each other.are antiparallel to each other.


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Chargaffs rulesChargaffs rules

Base composition varies among species.Base composition varies among species.

Base composition is constant for all cellsBase composition is constant for all cellsof anof an organism and within a species.organism and within a species.

The amount of adenine equals the amountThe amount of adenine equals the amount

of thymine. (A = T)of thymine. (A = T)The amount of cytosine equals theThe amount of cytosine equals the

amount ofamount ofguanine. (C = G)guanine. (C = G)

The amount of purine bases equals theThe amount of purine bases equals the

amount of pyrimidine bases.amount of pyrimidine bases.


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Within cells the standard structure of DNA is theWithin cells the standard structure of DNA is theB form.B form.

TheThe B formB form structure consists of two antiparallelstructure consists of two antiparallelpolynucleotide chains twisted around onepolynucleotide chains twisted around oneanother to form a double helix.another to form a double helix.

TheThe nitrogenous basesnitrogenous bases form the rungs in theform the rungs in the

center of the helix, withcenter of the helix, withadenine forming hydrogen bonds with thymineadenine forming hydrogen bonds with thymine

The helix is right-handed, and each chainThe helix is right-handed, and each chain

makes one complete turn every 34 angstroms.makes one complete turn every 34 angstroms.
http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.figgrp.638http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.figgrp.638http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.635http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.635http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.figgrp.645http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.figgrp.645http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.figgrp.645http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.section.635http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=stryer.figgrp.638


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Base pairing was worked out by trial andBase pairing was worked out by trial anderror. The distance between the sugar-error. The distance between the sugar-phosphate backbone groups is constantphosphate backbone groups is constant

ThereforeTherefore purine-purineurine-purine oror pyrimidine-yrimidine-pyrimidineyrimidine were not allowed because spacingwere not allowed because spacingwould be in inconsistent with datawould be in inconsistent with dataPurines = A and G (two organic rings)Purines = A and G (two organic rings)

Pyrimidines C and T ( one organic ring)Pyrimidines C and T ( one organic ring)Pu rin e- pyr imid ineu rin e- pyr imid ine base pairing would bebase pairing would be

consistent with X-ray dataconsistent with X-ray data


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Hydrogen bonding between purines andHydrogen bonding between purines andpyrimidines established the appropriate pairs andpyrimidines established the appropriate pairs andreinforced Chargaffs Rulesreinforced Chargaffs Rules2 hydrogen bonds between2 hydrogen bonds between

A and TA and T3 hydrogen bonds between3 hydrogen bonds between

G and CG and C


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Area of ResearchArea of Research

Construction of a small molecule whichConstruction of a small molecule whichbinds this DNA, if it is a organic moleculesbinds this DNA, if it is a organic moleculescalled as ligands, intercalators.called as ligands, intercalators.

Metal ions, present along with theMetal ions, present along with theintercalators are called asintercalators are called asmetallointercalator.metallointercalator.

The ligands which recognizes the specificThe ligands which recognizes the specific


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The earliest work on the DNA-binding ofThe earliest work on the DNA-binding of

metal centers focused onmetal centers focused ontris(phenanthroline) complexes of Ru, Cr,tris(phenanthroline) complexes of Ru, Cr,Zn, Ni, and Co. Photo physical and NMRZn, Ni, and Co. Photo physical and NMR

studies suggested that these complexesstudies suggested that these complexesbind to DNA viabind to DNA via

hydrophobic interaction in the minorhydrophobic interaction in the minor

groove and intercalation of agroove and intercalation of aphenanthroline ligand into the helix in thephenanthroline ligand into the helix in themajor groove.major groove.


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Intercalators are small organic moleculesIntercalators are small organic moleculesor metal complexes that unwind DNA inor metal complexes that unwind DNA inorder to pi-stack between the two baseorder to pi-stack between the two base

pairs.pairs.Eg. Two well known intercalating ligandsEg. Two well known intercalating ligands

are phi(9,10-phenanthrenequinoneare phi(9,10-phenanthrenequinone

diammine) and dppz.diammine) and dppz.


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Ru and dppz- based metallo-intercalatorsRu and dppz- based metallo-intercalators

have proven to be molecular lighthave proven to be molecular lightswitches for the detection of DNA.switches for the detection of DNA.

Rh intercalators have been shown to beRh intercalators have been shown to be

efficient agents for photoactivated DNAefficient agents for photoactivated DNAstrand cleavage.strand cleavage.


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Metallo intercalator and insertorMetallo intercalator and insertor

Metallo-intercalators enter the double helix viaMetallo-intercalators enter the double helix viathe major groove, with the intercalating ligandthe major groove, with the intercalating ligandacting as a new base pair. Intercalation results inacting as a new base pair. Intercalation results ina doubling of the rise and a widening of thea doubling of the rise and a widening of themajor groove at the binding site.major groove at the binding site.

Metallo insertors unwind the DNA and insertMetallo insertors unwind the DNA and inserttheir planar ligand between two intact base pairs,their planar ligand between two intact base pairs,

it ejects the bases of a single base-pair with theit ejects the bases of a single base-pair with theincoming ligand acting as a pi- stackingincoming ligand acting as a pi- stackingreplacement in the DNA base stack.replacement in the DNA base stack.


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Th e Best i s ye t to Co me

By,S . Ra j a lak sh m i .

DNA Metalcomplex

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