Amino Acids, Proteins and DNA

General structure of an amino acid NH2 CH CO2H R The R group can be a variety of different things depending on what amino acid it is. The simplest amino acid is glycine, where the R is an H NH2 CH2 CO2H Optical Activity All amino acids, except glycine, are chiral because there are four different groups around the C They rotate plane polarised light. H2N C CO2H CH3 H NH2 C HO2C CH3 H Some amino acids have an extra carboxylic acid or an amine group on the R group. These are classed as acidic or basic (respectively) amino acids NH2 C CO2H CH2 H CO2H Aspartic acid Naming amino acids You do not need to know any common names for the 20 essential amino acids. We should, however, be able to name given amino acids using IUPAC organic naming 2-aminobutanedioic acid NH2 CH2 CO2H (2-)aminoethanoic acid NH2 C CO2H CH2 H OH 2-amino-3- hydroxypropanoic acid H2N C CO2H H (CH2)4 NH2 Lycine (basic) 2,6-diaminohexanoic acid NH2 C CO2H CH2 H CO2H Zwitterions The no charge form of an amino acid never occurs. The amino acid exists as a dipolar zwitterion. H2N C CO2H H R H3N C + CO2 – H R Amino acids are often solids The ionic interaction between zwitterions explains the relatively high melting points of amino acids as opposed to the weaker hydrogen bonding that would occur in the no charge form. Zwitterion Acidity and Basicity The amine group is basic and the carboxylic acid group is acidic. H3N C + CO2 – H R H2N C CO2 – H R H3N C + CO2H H OH R – H+ OHH+ +NH3 -CH2 -CO2 – + HCl  Cl- NH3+ -CH2 -CO2H +NH3 -CH2 -CO2 – + NaOH  NH2 -CH2 -CO2 -Na+ +H2O Amino acids act as weak buffers and will only gradually change pH if small amounts of acid or alkali are added to the amino acids. Species in alkaline solution High pH Species in neutral solution Species in acidic solution Low pH. Other reactions of amino acids The carboxylic acid group and amine group in amino acids can undergo the usual reactions of these functional groups met in earlier topics. Sometimes questions refer to these. H2N C CO2H H CH3 + CH3OH H+ e.g. Esterification reaction

Dipeptides Dipeptides are simple combination molecules of two amino acids with one amide (peptide) link. For any two different amino acids there are two possible combinations of the amino acids in the dipeptide. Proteins NH CH C R O NH CH C R O NH CH C R O N CH C O O CH2 H H CH2 S CH3 N CH C CH2 O H HS N CH C CH2 O H CH H3C CH3 CH C CH3 O N H H Primary Structure of Proteins The primary structure of proteins is the sequence of the 20 different naturally occurring amino acids joined together by condensation reactions with peptide links Secondary Structure of a Protein. Secondary Structure: α-helix The R-groups on the amino acids are all pointed to the outside of the helix Secondary Structure: β-Pleated Sheet Structure of Proteins The secondary structure can also take the form of a β– pleated sheets The protein chain folds into parallel strands side by side The protein chain is held into a the pleated shape by Hydrogen bonds between the H of –N-H group and the – O of C=O of the amino acid much further along the chain in the parallel region . N Goalby chemrevise.org 3 Tertiary Structures of Proteins The tertiary structure is the folding of the secondary structure into more complex shapes. It is held in place by interactions between the R- side groups in more distant amino acids . These can be a variety of interactions including hydrogen bonding, sulphur- sulphur bonds and ionic interactions By Elizabeth Speltz (SpeltzEB) (Own work) [Public domain], via Wikimedia Commons CH2 H3C O H CH2 CH3 O H Hydrogen bonds Hydrogen bonds could form between two serine side chains in different parts of the folded chain. (Other amino acids chains can also hydrogen bond) C O C H CH2 OH H2N OH CH2 H3C C O – O CH3 H3N + ionic interactions Ionic interactions could form between acidic amino acids such as aspartic acid and basic amino acids such as lysine. There is a transfer of a hydrogen ion from the -COOH to the – NH2 group to form zwitterions just as in simple amino acids. CH2 H3C SH CH2 CH3 HS CH2 H3C S CH2 CH3 S C O C H CH2 OH H2N SH cysteine (cys) Sulphur bridges If two cysteine side chains end up near each other due to folding in the protein chain, they can react to form a sulphur bridge, which is a covalent bond. You don’t need to learn the details of these interactions on this page but understand the principles of how the tertiary structure is held in place.Proteins are polymers made from combinations of amino acids. The amino acids are linked by peptide links, which are the amide functional group. The 3D arrangement of amino acids with the polypeptide chain in a corkscrew shape is held in place by Hydrogen bonds between the H of –Nδ- —Hδ+ group and the –O of Cδ+=Oδ- of the fourth amino acid along the chain If proteins are heated with dilute acid or alkali they can be hydrolysed and split back in to their constituent amino acids. The composition of the protein molecule may then be deduced by using paper chromatography Hydrolysis of di-peptides/proteins N CH C O O CH2 H CH H3C CH3 CH C H CH3 O N H H CH C O O CH3 H3N + H H3N + CH C O O CH2 CH H3C CH3 H H+

+ Chromatography of Amino Acids A mixture of amino acids can be separated by chromatography and identified from the amount they have moved. Rf value = distance moved by amino acid distance moved by the solvent Each amino acid has its own Rf value Method Take chromatography paper and draw a pencil line 1.5cm from bottom. With a capillary tube put a small drop of amino acid on pencil line Roll up paper and stand it in a large beaker. The solvent in the beaker should be below the pencil line. Allow to stand for 20 mins and mark final solvent level Spray paper with ninhydrin and put in oven. If ninhydrin is sprayed on an amino acid and then heated for 10 minutes then red to blue spots appear. This is done because amino acids are transparent and cannot be seen.

Enzymes Enzymes are proteins. The active site is usually a hollow in the globular protein structure into which a substrate molecule can bond to the amino acid side chains through a variety of interactions including • Hydrogen bonding • Van der waals forces • Permanent dipole forces • Ionic interactions The interactions need to be strong enough to hold the substrate for long enough for the enzyme catalysed reaction to occur but weak enough for the product to be released CO2 – Hydrogen bonding Ionic interactions Van der waals forces active site substrate ser asp phe H3C Only substrate molecules with the right shape and correct positions of functional groups will fit and bind to the active site- called the lock and key hypothesis When the enzyme bonds to the active site it is called and enzyme-substrate complex stereospecific active site If the substrate is chiral then its likely that only one enantiomer will fit in the enzyme and so only one isomer will be catalysed Drugs as Enzyme Inhibitors Many drugs act as an enzyme inhibitor by blocking the active site. The inhibitor will often bind to the active site strongly so stopping the substrate attaching to the enzyme. (Some Inhibitors can also attach elsewhere on the enzyme but in doing so can change the shape of the active site which also stops its effectiveness) Computers can be used to help design such drugs

DNA Adenine (A) Cytosine (C) Guanine (G) Thymine (T) P O OH O – HO O OH OH HO CH2 H H H H H O OH OH HO The structures of these substances are given in the Chemistry Data Booklet. phosphate ion 2-deoxyribose (a pentose sugar) N N NH N NH2 N NH NH N NH2 O NH NH O O H3C N NH NH2 O Key molecules in DNA The 4 bases Nucleotides A nucleotide is made up from a phosphate ion bonded to 2-deoxyribose which is in turn bonded to one of the four bases adenine, cytosine, guanine and thymine O OH O P OH O O – N N N N NH2 O N OH O P OH O O – N NH2 O O OH O P OH O O – N N NH N NH2 O O OH O P OH O O – N NH O O H3C phosphate base sugar Although the structures will be given in the data sheet you need to learn which atoms on the base joins on to the sugar and how the sugar attaches to the phosphate ions. Sugar- phosphate chain A single strand of DNA (deoxyribonucleic acid) is a polymer of nucleotides linked by covalent bonds between the phosphate group of one nucleotide and the 2- deoxyribose of another nucleotide. This results in a sugar-phosphate- sugar- phosphate polymer chain with bases attached to the sugars in the chain. O OH O P O O O – N N N N NH2 O O N P OH O O – N NH2 O O OH O P OH O O – N N N N NH2 O N OH O P OH O O – N NH2 O -H2O DNA exists as two complementary strands of the sugar phosphate polymer chain arranged in the form of a double helix. Hydrogen bonding between base pairs leads to the two complementary strands of DNA. O OH O P OH O O – N N N N NH O H H O N OH O P OH O O – N NH O H O OH O P OH O O – N N O O CH3 H O OH O P OH O O – N N N N HN H Guanine pairs with cytosine by 3 hydrogen bonds Adenine pairs with thymine by 2 hydrogen bonds

The Pt(II) complex cisplatin is used as an anticancer drug. Pt 2+ Cl – Cl – H3N H3N Pt 2+ NH3 ClClH N3 cisplatin transplatin The cisplatin version only works as two chloride ions are displaced and the molecule joins on to the DNA. In doing this it stops the replication of cancerous cells. Cisplatin Cisplatin can also prevent the replication of healthy cells by bonding on to healthy DNA which may lead to unwanted side effects like hair loss. Society needs to assess the balance between the benefits and the adverse effects of drugs, such as the anticancer drug cisplatin. Cisplatin prevents DNA replication in cancer cells by a ligand replacement reaction with DNA in which a dative covalent bond is formed between platinum and a nitrogen atom on guanine Pt NH3 NH3 N NH NH N NH2 O The N and O atoms marked in red can’t bond to cis-platin as they are involved in the bonding within the DNA