Amino Acids, Peptides & Proteins
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Amino Acids, Peptides & Proteins. a -amino acid:. Amino Acids. Are >500 naturally occurring amino acids identified in living organisms Humans synthesize 10 of the 20 they use. The other 10 are called essential amino acids. Amino Acids, Peptides & Proteins. Peptides & proteins:

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Amino acids peptides proteins

Amino Acids, Peptides & Proteins

a-amino acid:


Amino acids peptides proteins

Amino Acids

  • Are >500 naturally occurring amino acids identified in living organisms

  • Humans synthesize 10 of the 20 they use. The other 10 are called essential amino acids.


Amino acids peptides proteins

Amino Acids, Peptides & Proteins

  • Peptides & proteins:

  • Derived from amino acids through peptide or amide bonds.

  • The amine and acid ends of amino acids couple to form amide (peptide) bonds

  • in peptides/proteins/enzymes.

  • Proteins fold into well-defined structures. The hydrophobic residues

  • segregate to the water-free interior, while the polar/charged residues favor

  • the exterior.


Amino acids peptides proteins

Peptides: Coupling AAs Together

  • Peptides & Proteins: Linear oligomers of the 20 amino acids

  • Peptides ≤ 20 amino acids; Proteins > 20 amino acids

  • Functions:

  • Catalysis - enzymes

  • Membrane channels

  • Structural support (boundaries)

  • Regulate metabolites (storage & transport)

  • Antibodies; cellular signaling (recognition & binding)


Amino acids peptides proteins

Aspartame

  • Discovery story:

  • In 1965 by Jim Schlatter

  • working on discovering new

  • treatments for gastric

  • ulcers.

  • Made a dipeptide intermediate,

  • which he spilled on his hand

  • Tested the dipeptide in coffee

Aspartame

  • 4 calories per gram

  • 180 times sweeter than sugar


Amino acids peptides proteins

Aspartame: A Dipeptide

Two main constituents:

Phenylalanine

Aspartic acid

Goal:

Make the methyl

ester of phenylalanine

2. Make a peptide (amide)

bond between phenylalanine

and aspartic acid

Overall - two main steps to this synthesis


Amino acids peptides proteins

Dipeptides: Coupling of 2 AAs

Consider the synthesis of the dipeptide val-ala (valine-alanine):

  • Coupling of amino acids is an application of nucleophilic acyl substitution

  • Issue of selectivity arises:

  • val + ala  val-ala + ala-val +

  • val-val + ala-ala

  • A mixture of 4 possible amide

  • products


Amino acids peptides proteins

Merrifield’s Solid-Phase Synthesis

In order to get the desired peptide (val-ala), the appropriate NH2 and CO2

units must be joined.

The selectivity is accomplished through the use of protecting groups.

Merrifield’s approach:

Protect N-terminus of valine

Protect C-terminus of alanine

Couple valine and alanine

Deprotect to get dipeptide


Amino acids peptides proteins

Merrifield’s Solid-Phase Synthesis

1. Protection of valine’s N-terminus:


Amino acids peptides proteins

Merrifield’s Solid-Phase Synthesis

2. Protection of alanine’s C-terminus:

Attach the C-terminus to a plastic bead (solid-phase synthesis!)

  • Benefits of solid-phase:

  • Ease of attachment

  • Ease of removal; just filter away from product solution


Amino acids peptides proteins

Merrifield’s Solid-Phase Synthesis

3. Couple valine and alanine:


Amino acids peptides proteins

Merrifield’s Solid-Phase Synthesis

3. Deprotection of Fmoc & bead:


Amino acids peptides proteins

Proteins

  • Amino acid polymers; when long enough, they fold back on themselves to

  • create intricate, well-defined 3D structures

  • The structure of a protein specifies its function.

  • The AA sequence specifies its structure.

  • The AA chain typically adopts regional sub-structures which sum together

  • to deliver the overall structure of the protein.

  • Forces/Factors that dictate protein folding:

  • Planarity of amide bonds

  • H-bonding

  • Hydrophobic interactions

  • Electrostatic Attraction

  • Disulfide linkages


Amino acids peptides proteins

Proteins

1. Planarity of amide bonds:


Amino acids peptides proteins

Proteins

2. H-bonding:

H-bond worth ~ 5 kcal/mol

H-bonds orient the chain


Amino acids peptides proteins

Proteins

3. Hydrophobic Interactions:

Lots of hydrophobic interactions

between Rs and H2O -

unstable

Protein folds to “clump” R

groups together in the

interior of protein to avoid

H2O - very energetically

favored


Amino acids peptides proteins

Proteins

4. Electrostatic Attraction:


Amino acids peptides proteins

Proteins

5. Disulfide Linkages:

  • Covalent S-S

  • Drastically alters shape

  • Worth ~ 50 kcal/mol


Amino acids peptides proteins

Proteins

  • Overall, these 5 structural/energetic features leads to the final 3D protein

  • structure. However, predicting the structure from the amino acid sequence

  • is still a challenge.

  • Hierarchy of Structural Elements of Proteins

  • Primary structure: AA sequence

  • Secondary structure: discrete sub-structural elements (modules)

    a-helix & b-sheet

a-helix: see board for depiction

Note:

Internal H-bonding

The way the side chains line up

3.6 AAs per turn

b-sheet: see board for depiction

Note:

Chain-to-chain H-bonding

Alternating (up-down, up-down)

Pattern of R groups


Amino acids peptides proteins

Proteins

  • Hierarchy of Structural Elements of Proteins

    3. Teritary Structure: the individual secondary structural elements organized

    in 3D.

    See board for depiction.

    4. Quaternary Structure: non-covalent complexation of different proteins.


Amino acids peptides proteins

Lipids

  • Structurally diverse, derived from living organisms

  • Functional theme is hydrophobicity - water avoiding due to long alkyl chains

  • Often found at the interface of aqueous compartments

  • 3 Major Classes of Lipids:

  • Fats and oils

  • Phospholipids

  • Cholesterol & derivatives (steroids)


Amino acids peptides proteins

Lipids

Fats & Oils

Derived from glycerol and fatty acids:

Weak intra-

molecular

attractive forces

between chains


Amino acids peptides proteins

Lipids

  • Fats & Oils

  • In order for a fat to melt, these weak dispersive forces must be broken.

  • More contacts, the better the packing and the higher the m.p. of the fat

  • Less contacts, worse packing of chains, the lower the m.p.

    Unsaturated Fats:

Oils are polyunsaturated - lots of

alkenes & have low mp due to less packing

Butter has very little unsaturated & has

higher mp


Amino acids peptides proteins

Lipids

Soaps & Detergents

  • Hydrolyzed fats

  • A long chain carboxylate molecule:


Amino acids peptides proteins

Lipids

Soaps & Detergents

In H2O, forms

a micelle.

Grease & dirt get

trapped in the interior.

Micelle is H2O soluble

so can wash out dirt.


Amino acids peptides proteins

Lipids

2. Phospholipids:

  • Have hydrophobic and hydrophilic regions

  • Forms membranes

  • Precursors to prostaglandins


Amino acids peptides proteins

Lipids

2. Phospholipids:

  • Forms membranes: self-organize at certain concentrations to form bilayers

  • Membranes are largely impermeable to charged species that exist in

    biological environments.

Cell membrane


Amino acids peptides proteins

Lipids

3. Cholesterol & Steroids

Cholesterol:

27 carbons

4 rings

8 stereocenters

Derived from terpenes

Cholesterol is a precursor to several steroidal hormones:

Testosterone (male hormone)

Estrone (female hormone)


Amino acids peptides proteins

Lipids

Cholesterol is a precursor to several steroidal hormones:

Testosterone (male hormone)

Estrone (female hormone)

These hormones operate at the genetic level (turn genes on and off) to

control biochemistry. They are recognized by specific protein receptors.


Amino acids peptides proteins

Antioxidants & Chocolate

  • Antioxidants:

  • Protect against cardiovascular disease, cancer and cataracts

  • Thought to slow the effects of aging

  • Chocolate:

  • High levels of antioxidants - complex mixtures of phenolic comounds

  • By weight, has higher concentration of antioxidants than red wine or

  • Green tea

  • 20x higher concentration of antioxidants than tomatoes

Dark chocolate has more than 2x the level of antioxidants as milk chocolate.

Side note: The main fatty acid in chocolate, stearic acid, does not appear to raise blood cholesterol levels the way other saturated fatty acids do.


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