Proteins and peptides are involved in many normal and disease-related biological processes, including biological structure, enzyme catalysis, hormone regulation, antibiotic action, Alzheimer’s disease, mad-cow disease (the chapter story), etc.

Review of carboxylic acids and amines

Amino acids (Table 20.1)
—building blocks of peptides (i.e., "short proteins") and proteins
—a carboxylic acid (-COOH) that contains an amino group (-NH₂)
—a -amino acids: the amino group is bound to the "a -carbon", which the carboxylic acid is also bound to.

Side chains
hydrophobic (non-polar)
    • aliphatic, e.g., H (Gly), methyl (Ala), isopropyl (Val), isobutyl (Leu), sec-butyl (Ile), Pro (with a ring structure)
    • aromatic, e.g., benzyl (Phe), para-phenyl (Tyr), indole-methylene (Trp)

 hydrophilic (polar)
    • acidic: ethanoic (Asp) and its amide (Asn) and propanoic (Glu) and its amide (Gln)
    • neutral (alcohol-, thiol-, thiol ether-containing, and amide): hydroxymethyl (Ser) and sec-hydroxymethyl (Thr), and thiomethyl (Cys) and methylthioethyl (Met, hydrophobic). Cys and Met are the only amino acids that contain S.
    • basic: amino (Lys), guanidinyl (Arg), imidazole (His)

MSG: mono-sodium glutamate, when one of the two carboxylic acid groups is neutralized with NaOH.

Stereoisomers of amino acids
L-amino acids have the 4 groups, amino, carboxyl, the side chain, and the hydrogen on the a -carbon arranged as below

  L-amino acid (NH₂ on the left side of COOH)

D-amino acid: NH₂ and COOH in L-amino acid switch positions.

Zwitterions— internal (intramolecular) salts (with both positive and negative charges present on the same molecule)

What will happen when you mix a carboxylic acid with an amine?
        R–COOH + R’–NH₂ ® R–COO^–(R’–NH₃⁺) a salt!!

Thus, for an amino acid
        H₂N–CHR–COOH ® ⁺H₃N–CHR–COO^–

Isoelectric points (IP)— at which the charges in an amino acid are balanced
• pH < IP, positively charged (both the amino and the carboxylic acid groups are protonated).
• pH > IP, negatively charged (the carboxylic acid is deprotonated).

        pH < IP                       pH = IP                    pH > IP
⁺H₃N–CHR–COOH ® ⁺H₃N–CHR–COO^– ® H₂N–CHR–COO^–

Peptides— amino acids condensed together via the amino group on one and the carboxylic acid group on the other by forming an amide bond –CO–NH– (a peptide bond)

                                        N-terminal (residue 1)                       C-terminal (residue #n)

The reverse reaction is peptide hydrolysis (hydro, water; lysis, cleavage).

Examples of peptides
NutraSweet^® (about 200 times sweeter than sucrose) is the methyl ester of Asp-Phe (Structure? See P. 513)
    ***A sweetener not for people with phenylketonuria***

Peptide hormones (Table 20.2, P. 600)
oxytocin and vasopressin: cyclic nonapeptides with a disulfide bond differ by two amino acid residues, but very different functions; the former stimulates milk ejection and sensation, and contraction of the smooth muscle while the latter is an antidiuretic which stimulates excretion of water by kidneys.

enkephalins: pentapeptides associated with relief of pain

angiotensin II: an octapeptide causing constriction of arteries

bradykinin: a nonapeptide, triggering pain, lowering blood pressure, involved in inflammation, etc.

Insulin ("Chemistry with us". P. 615)

antibiotics and inhibitors: penicillin precursor, bacitracin, etc.

Primary structure of proteins: order of amino acids in proteins, which is listed by convention from the N-terminal to the C-terminal residue.

For a peptide with one each of n different amino acid, the number of constitutional isomers is n! (n fractorial, = 1 ´ 2 ´ 3 ´ …´ n.
Dipeptide: 2 isomers, e.g., Asp–Phe and Phe–Asp
Tripeptide: 6, e.g., ABC, ACB, BAC, BCA, CAB, and CBA.
 

Secondary structure of proteins  Alpha helix— coiled into a right-handed spiral shape with H-bond between CO of #n amino acid and NH of #n+4 amino acid with 3.6 residues per turn, and can intertwine into fibrous proteins

beta strands/sheets— peptide chains with a zigzag structure (strands), and can assembled together (parallel or antiparallel) via H-bonds to form sheets

Tertiary structure of proteins: folding of proteins into 3-dimensional structures via hydrophobic interactions, disulfide –S–S– bridge between two Cys residues when oxidized (PP. 600, 607), hydrogen bonds, and salt bridges (e.g., myoglobin)

Quaternary structure of proteins: packing of "subunits" of proteins

e.g., hemoglobin (Hb)— 2 a subunits and 2 b subunits

**Review hemoglobin and myoglobin in a previous lecture!!
 

Fibrous proteins  a -keratins: structural components of hair, horn, hooks, nails, skin, and wool, almost entirely in a -helix conformation with a pair of a -helices forming a supercoil or superhelix structure. A pair of supercoil form a protofibril, linked by disulfide bonds.

Collagen: The most abundant protein in vertebrates and the major stress-bearing component of connective tissues, which has a triple helix structure

b -keratins: in bird feathers and reptile scales, almost completely composed of b -sheets structure.

Silk fibroin: by insects and is one of the most strong materials.

Globular proteins: Do not aggregate into macroscopic structure as fibrous proteins, and are involved in biological catalysis and many other functions, such as proteases in our digestive system, hemoglobin and myoglobin, etc.

Review hemoglobin and mutation (e.g., sickle-cell anemia)

Denaturation of proteins— unfold of native proteins caused by

(a) heat,
(b) UV and ionizing radiations,
(c) breaking of disulfide bonds (reduction),
(d) denaturing agents such as urea and alcohol (70% as antiseptic agent),
(e) extreme pHs (acidic and basic), and
(f) heavy metal ions Pb²⁺, Hg²⁺, and Ag⁺ which can form strong bonds with Cys residue (2 R–SH + M^+/2+ ® R–S–M–S–R + 2H⁺).