Chapter 3 - Amino acids(1).pptx

CHAPTER 3: AMINO ACIDS & PEPTIDES Week 3 CHEM311 Chapter Outline 3-1 Amino Acids: structure, types and classification 3-2 Individual Amino Acids: Structures and Properties 3-3 Ionization of amino acids (pka and pI) 3-4 The Peptide Bond Amino Acids: structure α-amino acid: a compound that contains bo...

CHAPTER 3: AMINO ACIDS & PEPTIDES Week 3 CHEM311 Chapter Outline 3-1 Amino Acids: structure, types and classification 3-2 Individual Amino Acids: Structures and Properties 3-3 Ionization of amino acids (pka and pI) 3-4 The Peptide Bond Amino Acids: structure α-amino acid: a compound that contains both an amino group and a carboxyl group: α-carbon: carbon adjacent to carboxyl group and the carbon bound to the amino group and R-group R group gives identity to amino acid Amino acids are tetrahedral and chiral (except glycine because R group is H) Chiral: two steroisomers exist based on where the amino group is present on the α-carbon ; L (left) or D(right). Based on similarity to glyceraldehyde with respect to where the OH group is found on the chiral carbon Majority of biological systems produce L-isomer: few exceptions, particularly in bacterial world Amino Acid: Types  20 ‘standard’ encoded amino acids (the one you must know)  Note: really there are 22 amino acids, 2 of these are non-canonical and have special translation mechanisms  Over 450 are known, these are standard amino acids that undergo post-translation modification. Amino Acid: classification  based on the type or characteristic of R-group;  Aliphatic, aromatic, cyclic  acidic, basic, sulfur, amide bonds  polar or non-polar  Based on site of attachment of the functional group  α-, β-,γ-, δ-…greek notation Non-polar amino acids (9 of them) Gly, Ala, Val, Leu, Ile: aliphatic listed in order of increasing hydrophobicity Met: sulfur in side chain Phe and Trp: aromatic ring, Trp also has indole ring Pro: cyclic structure and amine is 2o Polar (uncharged) amino acids: (6 of them) Ser, Thr: hydroxyl group in side chain Cys: thiol group (-SH) in side Tyr: hydroxyl group bonded to aromatic hydrocarbon group Asn and Gln: contain amide bonds in side chain Disulfide Bond formation (reaction of Cysteines) Polar (charged amino acids): known as Acidic and basic amino acids (5 of them) Side chain has a negative charge at pH 7 Side chain has a positive charge at pH 7 guanidino group Imidazole group Acidity:  -COOH Groups the average pKa of an α-carboxyl group is 2.19, which makes them considerably stronger acids than acetic acid (pKa 4.76) the greater acidity of the α -amino acid carboxyl group is due to the electronwithdrawing inductive effect of the -NH3+ group pH < pka = protonated pH > pka = deprotonated Aspartic acid Glutamic acid Basicity  -NH3+ groups: The average value of pKa for an  -NH3+ group is 9.47 Guanidine Group The side chain of arginine is a considerably stronger base than an aliphatic amine basicity of the guanido group is attributed to the large resonance stabilization of the protonated form relative to the neutral form Imidazole Group The side chain imidazole group of histidine is a heterocyclic aromatic amine pH < pka = protonated pH > pka = deprotonated Histidine Lysine Arginine Amino acid summary 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 (look at the structure of the molecules) 5. 3, and 1-letter codes in Table 3.1. Uncommon Amino Acids: post translation modification Each derived from a common amino acid by a modification hydroxylysine and hydroxyproline are found only in a few connective tissues such as collagen thyroxine is found only in the thyroid gland Common Amino Acids 15 Ionization of Amino Acids Remember, amino acids without charged groups on side chain exist in neutral solution as zwitterions with no net charge 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 Titration of Acetic Acid Titration of Amino Acids - Glycine Isoelectric pH, pI: the pH at which the majority of molecules of a compound in solution have no net charge Isoelectric pH (pI) Isoelectric pH, pI: the pH at which the majority of molecules of a compound in solution have no net charge the pI for glycine, for example, falls midway between the pKa values for the carboxyl and amino groups pI = /2 pI =(2.34 + 9.60 )/ 2 = 5.97 Isoelectric pH values for the 20 protein-derived amino acids are given in Table 3.2 Titration of Amino Acids - Aspartate Titration of Amino Acids - Histidine When an amino acid is titrated, the titration curve represents the reaction of each functional group with the hydroxide ion Titration of His with NaOH pI calculation for more complex amino acids How to calculate pI for amino acids (or other molecules) that have more than 2 ionizable groups??? Practice – pI for Glutamic acid What is the isoelectric point of glutamic acid, given: pKa (α-COOH) = 2.19, pKa (α-NH2) = 9.67, pKa (R) = 4.25? Strategy Identify the charge on the amino acid above and below each pKa (for the acid, amine and side chain if necessary) Identify the pH region where the acid is neutral Use the two pKa values that bound the neutral region to calculate the pI What is the isoelectric point of glutamic acid, given: pKa (α-COOH) = 2.19, pKa (α-NH3) = 9.67, pKa (R) = 4.25? Identify the charge on the amino acid above and below each pKa : pH 9.67 COOH is -1, R is -1 and NH3 is 0: so net charge -2 Identify the pH region where the acid is neutral: between pH 2.19 and 4.25 Use the two pKa values that bound the neutral region to calculate the pI: pI = (2.19+4.25)/2 = 3.22 Practice: solution What is the isoelectric point of glutamic acid, given: pKa (α-COOH) = 2.19, pKa (α-NH3) = 9.67, pKa (R) = 4.25? remember: pH < pka = protonated pH > pka = deprotonated Identify the charge on the amino acid above and below each pKa : pH 9.67 COOH is -1, R is -1 and NH3 is 0: so net charge -2 Identify the pH region where the acid is neutral: between pH 2.19 and 4.25 Use the two pKa values that bound the neutral region to calculate the pI: pI = (2.19+4.25)/2 = 3.22 pI calculation for peptide https://www.youtube.com/watch?v=vyDyBUspRsg The peptide bond 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 Dehydration reaction (loss of H2O) The peptide bond / chain Growing polypeptide chain… Geometry of Peptide Bond 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) the hybrid has considerable C-N double bond character and rotation about the peptide bond is restricted Geometry & Resonance of Peptide Bond Planar: 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 a peptide bond is most accurately represented as a resonance structure C-N double bond character: rotation about the peptide bond is restricted Physiologically active small peptide