Chapter 22 - Lecture notes 22 PDF

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Isabelle Engelberg Falzone Organic Chemistry II Chapter 22 Amino Acids, Peptides and Proteins GOALS 1. You should know the different types of amino acid side chains (acidic, basic, hydrophobic, polar); 2. The pI of an amino acid is and how to determine it 3. That 19/20 of the L‐ amino acids are chiral and that all but cysteine are in the S‐ configuration; Ile and Thr have chiral side chains 4. Primary, secondary, tertiary, and quaternary structure and how to recognize α helices and β‐ sheets (parallel and anti‐ parallel); post‐ translational modifications; disulfide bonds 5. Dihedral angles; allowed dihedral angles—Ramachandran plots indicate allow bond angles based on steric interactions. 1. TYPES OF SIDE CHAINS - side chain = other side of NH3 Acidic  Asp (D)  Glu (E) Basic  Lys (K)  Arg (R) – most basic  His (H) Nonpolar (Hydrophobic)  Gly (G)  Ala (A)  Val (V)  Leu (L)  Ile (I)  Met (M)  Pro (P)  Phe (F)  Trp (W) Polar  Asn (N)  Gln (Q)  Ser (S)  Thr (T)  Tyr (Y)  Cys (C)

2. pI OF AMINO ACIDS  pI = pH at which there is no net charge

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o positive charge exactly balances negative charge for neutral amino acids, pI = average of pKaNH3+ and pKaCOOH o does not have an ionizable side chain for amino acids that have an ionizable side chain, pI = avg of pKas of similarly ionizing groups for basic side chains, pI = average of 2 highest pKas (2 positively charged) for acidic side chains, pI = average of 2 negatively charged pKas o pKa values lower than the –NH3+ group to have no net charge, we need to be halfway btw the 2 acidic or basic groups to get one negative or positive charge to balance the existing positive (amino) or negative (carboxylate) charge

3. CHIRALITY  19/20 L-amino acids are chiral o only glycine is not chiral (2 H’s) o act as enantiomers  all in S configuration except cysteine (S is higher priority than O) o use D and L notation o draw amino acid as Fischer projection with carboxyl group at top and R group on bottom o if amino group (NH3+) is on the left = L o most amino acids found in nature are in the L configuration o L = S, D = R o all of the rest side chains have C attached to a C or single bonded O = lower priority than double bonded O  Ile and Thr have chiral side chains 4. PRIMARY, SECONDARY, TERTIARY AND QUATERNARY STRUCTURE  primary structure = amino acid sequence and location of all disulfide bridges  secondary structure = regular conformation adopted by the backbone o α-helix and β-sheet  tertiary structure = 3D structure of the entire protein  quaternary structure = >1 polypeptide chain, the way the individual polypeptide chains are arranged with respect to one another SECONDARY STRUCTURE  describes the repetitive conformations assumed by segments of the backbone chain of a peptide or protein  factors that determine secondary structure o regional planarity about each peptide bond (result of partial DB character of amide bond) o minimizing energy by maximizing the number of peptide groups that engage in H bonding (btw the carbonyl O of one amino acid and the amide H of another) o need for adequate separation btw neighboring R groups to avoid steric strain and repulsion of like charges

α-helix: backbone of the polypeptide coils around the long axis of the protein molecule o substituents on the α-carbons of the amino acids protrude outward from helix to minimize steric strain o helix is stabilized by H bonds – each amide H is bonded to a carbonyl O 4 amino acids away o right handed due to L-configuration o can be stretched (wool, fibrous protein of muscle)  β-pleated sheet: polypeptide backbone is extended in a zigzag structure resembling a series of pleats o H bonding occurs btw neighboring peptide chains o neighboring peptide chains can run in the same direction (parallel) or opposite directions (antiparallel) o substituents must be small in order to be close enough for H bonding o almost fully extended so cannot be stretched (silk, spider webs) DISULFIDE BONDS/POST-TRANSLATIONAL MODIFICATIONS  when thiols (R-SH) are oxidized under mild conditions, they form a disulfide bond (S-S)  common oxidizing agent is Br2 in a basic solution  disulfides can be reduced to thiols  cysteine contains a thiol group, so 2 cysteine molecules can be oxidized to a disulfide = cystine  2 cysteines in a protein can be oxidized to a disulfide = disulfide bridge o only covalent bonds that are found btw nonadjacent amino acids in peptides and proteins o contribute to overall shape of a protein by linking cysteines found in different parts of the peptide backbone  insulin o insulin is a polypeptide with 2 peptide chains o the chains are connected to each other by 2 interchain disulfide bridges (btw 2 chains) o insulin also has an intrachain disulfide bridge (within a chain) 

5. DIHEDRAL ANGLES  not all combinations of backbone dihedral angles (φ and ψ) are allowed because of steric clashes  Ramachandran plot = the map of allowed pairs (ψ vs. φ) o indicate that 2 types of backbone conformations are acceptable:  extended (β-sheet)  right-handed helical (α-helix)...