Lecture 6: Amino Acids and Peptides PDF

Lecture 6 Amino acids and Peptides  TOPIC OUTLINE Amino acids: Structure and Properties Ionization of Amino Acids Peptide Bonds Peptides with Physiological Activity AMINO ACIDS a compound that contains both an amino group and a carboxyl group R  -Amino aci...

Lecture 6 Amino acids and Peptides  TOPIC OUTLINE Amino acids: Structure and Properties Ionization of Amino Acids Peptide Bonds Peptides with Physiological Activity AMINO ACIDS a compound that contains both an amino group and a carboxyl group R  -Amino acid has an amino H2N-C-COOH group attached to the carbon adjacent to the H carboxyl group  -carbon also bound to side chain group, R (gives identity to amino acid) Two steroisomers of amino acids are designated L- or D-  AMINO ACIDS Twenty amino acids are commonly found in proteins. These amino acids contain a variety of different functional groups: Alcohols (R-OH) Phenols(Ph-OH) Carboxylic acids (R-COOH) Thiols (R-SH) Amines (R-NH2) Amide (R-CONH2)  20 Common Amino Acids Group A: Nonpolar side chains- Ala, Val, Leu, Ile, Pro. Phe, Trp, Met. Ala, Val, Leu, Ile, Pro- contain aliphatic hydrocarbon group. Pro has cyclic structure. Phe- hydrocarbon aromatic ring. Trp- Indole ring side chain, aromatic. Met- Sulfur atom in side chain.  20 Common Amino Acids Group B: Neutral Polar side chains- Ser, Thr, Tyr, Cys, Glu, Asn Ser, Thr- Side chain is polar hydroxyl group Tyr- hydroxyl group bonded to aromatic hydrocarbon group Cys- Side chain contains thiol group (-SH) Gln, Asn- contain amide bonds in side chain  20 Common Amino Acids Group C: Acidic Side Chains: Glu, Group D: Basic side chains: His, Lys, Arg Asp Side chains are positively charged at pH 7 - Both have a carboxyl group in side Arg- side chain is a guanidino group chain His- side chain is an imidazole group - Can lose a proton, forming a carboxylate ion Lys- side chain NH3 group is attached to an aliphatic hydrocarbon chain - These amino acids are negatively charged at neutral pH  Amino Acids Important structural features: 1. All 20 are  -amino acids 2. For 19 of the 20, the  -amino group is primary; for proline, it is secondary 3. With the exception of glycine, the a- carbon of each is a stereocenter 4. Isoleucine and threonine contain a second stereocenter 20 Common Amino Acids Ionization of Amino Acids The process by which an atom or a molecule acquires a negative or positive charge by gaining or losing electrons. Amino acids are amphoteric molecules. Amphoteric – can act as either an acid or a base Both groups have conjugate acid-base forms depending on the pH of the solution Ionization of Amino Acids In amino acid, carboxyl group (-) and amino group (+) are charged at neutral pH. In free amino acids  -carboxyl, and a-amino groups have titratable protons. Some side chains do as well  Ionization of Amino Acids pKa – apparent dissociation constant( refers as to how acidic or basic a given hydrogen atom in a molecule is) pH – power of Hydrogen (refers as to how acidic or basic a solution is) At pH of 2, 50% of COOH are in conjugate acid form and 50% are in its conjugate base form. At pH of solution 2, COOH has -1 charge  Ionization of Amino Acids At low pH, proton concentration [H+]is high. Therefore, both amines and carboxylic acids are protonated. (-NH3+ & -COOH) At high pH, proton concentration is low. Therefore, both amines and carboxylic acids are deprotonated. (-NH2 & - COO-) At neutral pH, amines are protonated(-NH3+) and carboxylates are deprotonated(-COO-) (Zwitterion forms at neutral charge) ISOELECTRIC POINT (pI) the pH at which the majority of molecules of a compound in solution have no net charge At pH 5.5, almost all molecules would be at 0 net charge or in zwitterion form Electrophoresis the process of separating compounds on the basis of their electric charge Electrophoresis of amino acids can be carried out using paper, starch, agar, certain plastics, and cellulose acetate as solid supports in paper electrophoresis, a paper strip saturated with an aqueous buffer of predetermined pH serves as a bridge between two electrode vessels IONIZATION OF AMINO ACIDS EXAMPLES: Cysteine IONIZATION OF AMINO ACIDS EXAMPLE: pI = 2.35 + 9.87 / 2 = 6.11 pH < 2.35 pH > 2.35, < 9.87 pH > 9.87 +1 0 -1  IONIZATION OF AMINO ACIDS EXAMPLE: Cysteine pKa1 = 1.71 ; pKa2 = 10.78 ; pKa3 = 8.33 pI = 1.71 + 8.33 / 2 = 5.02 pH < 1.71 pH > 1.71 < 8.33 pH > 8.33 < 10.78 pH > 10.78 +1 0 -1 -2 IONIZATION OF AMINO ACIDS EXAMPLE:  Peptide Bonds Individual amino acids can be linked by forming covalent bonds. Peptide bond: the special name given to the amide bond between the  -carboxyl group of one amino acid and the  -amino group of another amino acid  Geometry of Peptide Bonds the four atoms of a peptide bond and the two alpha carbons joined to it lie in a plane with bond angles of 120°about C and N to account for this geometry, a peptide bond is most accurately represented as a hybrid of two contributing structures (resonance structures)  Geometry of Peptide Bonds peptide: the name given to a short polymer of amino acids joined by peptide bonds; they are classified by the number of amino acids in the chain dipeptide: a molecule containing two amino acids joined by a peptide bond tripeptide: a molecule containing three amino acids joined by peptide bonds polypeptide: a macromolecule containing many amino acids joined by peptide bonds protein: a biological macromolecule of molecular weight 5000 g/mol or greater, consisting of one or  Peptides with Physiological Activity L-Carnosine comes from meat – useful in the prevention of damage caused by too much sugar Concentrated in muscles – used in the treatment of complications of diabetes such as Peptides with Physiological Activity  Seatwork 1. Draw the ionization of each amino acids in varying pH conditions 2. Compute the pI of each amino acids. 3. Which amino acids migrate towards the cathode when electrophoresis is carried out at pH 7.1? 4. Which amino acids migrate towards the anode when