Chapter 24 Lecture Notes - CEM252 at MSU Fall 1996

Chapter 24: Amino Acids and Proteins

Amino Acid
Compound with amino functional group and carboxylic acid functional group
a-amino acids
amine and carboxyl separated by 1 carbon atom
b-amino acids
amine and carboxyl separated by 2 carbon atoms... Chapter 24 - Slide 1

Protein-Derived Amino Acids

Protein - biological polymer of a-amino acids

Simplest protein derived amino acid (aa) - glycine (only achiral protein-derived aa)

Chapter 24 - Slide 2

Chirality of amino acids

Only one configuration found naturally

Chapter 24 - Slide 3

Natural AA Sidechains (R groups): Non-polar

Chapter 24 - Slide 4

Natural AA Sidechains (R groups): Polar, neutral

Chapter 24 - Slide 5

Natural AA Sidechains (R groups): Polar, acidic

Chapter 24 - Slide 6

Natural AA Sidechains (R groups): Polar, basic

Chapter 24 - Slide 7

Acid-Base Properties of Amino Acids

Amino AcidpKa a-CO2HpKa b-CO2HpKa a-NH3+
Aspartic Acid2.103.869.82

Chapter 24 - Slide 8

Significance of pKa

Chapter 24 - Slide 9

Forms of Amino Acid Present as a Function of pH

Chapter 24 - Slide 10

Buffer Regions

Chapter 24 - Slide 11


Tyrosine has an a-CO2H pKa of 2.20, and a-NH3+ pKa of 9.11, and a sidechain pKa of 10.07 - sketch a titration curve and give the structure of the major form or forms present at all equivalence and half-equivalence points.

Chapter 24 - Slide 12

Isoelectric Point

Isoelectric point (pI) - pH at which molecule has no net charge
(find by averaging pkas on either side of neutral form)
Chapter 24 - Slide 13

Isoelectric Precipitation

Amino acids with net charges repel each other and do not easily crystallize from solution - solubility is lowest at the isoelectric point

Chapter 24 - Slide 14


A method for separating charged compounds in an electric field

Chapter 24 - Slide 15


Dietary protein provides aas not made in our systems - these are called essential
Essential Amino AcidsNonessential Amino Acids
isoleucineaspartic acid
leucineglutamic acid
Chapter 24 - Slide 16

Polypeptides and Proteins

Proteins and polypeptides are chains of aa's

Dipeptide - 2 amino acids
Tripeptide - 3 amino acids ...
Polypeptides have 10 or more amino acids
Proteins have 100s or more amino acids

Chapter 24 - Slide 17

Amino Acid Connections

Chapter 24 - Slide 18

Peptide Bond Geometry

Peptide bonds are planar due to conjugation of nitrogen lone pair with carbonyl
Peptide bond movie

Chapter 24 - Slide 19

Protein Structural Descriptions

Primary Structure
sequence of amino acids
Secondary Structure
local three-dimensional patterns
Tertiary Structure
three-dimensional shape of an amino acid chain
Quaternary Structure
three-dimensional shape of multiple amino acid chains
Chapter 24 - Slide 20

Primary Structure Determination

Step 1: Amino Acid Analysis
Protein is hydrolyzed in strong acid or base at high temperatures
Mixture of amino acids generated by protein hydrolysis is analyzed by chromatography

Step 2: Sequence Analysis
protein cleaved into polypeptides
polypeptides subjected to amino acid analysis or Edman degradation

Chapter 24 - Slide 21

Sample Hydrolysis

Chapter 24 - Slide 22

Sequence Analysis

Chapter 24 - Slide 23

Cyanogen Bromide Cleavage

Chapter 24 - Slide 24

Edman Degradation

This process can be repeated ~20-30 times
Long polypeptides require cleavage to small units which can be individually sequenced

Chapter 24 - Slide 25



What is the structure of the original peptide?

Chapter 24 - Slide 26

Secondary Structure

Common local conformations:

Stabilized by:

Chapter 24 - Slide 27


alpha helix movie
Chapter 24 - Slide 28

Beta-Pleated Sheet

beta sheet movie
Chapter 24 - Slide 29

Tertiary Structure

Stabilized by:

Chapter 24 - Slide 30

Quaternary Structure

Forces holding protein chains together:

Chapter 24 - Slide 31

Polypeptide Synthesis


Chapter 24 - Slide 32

Polypeptide Synthesis

Chapter 24 - Slide 33

Linear Polypeptide Synthesis

Chapter 24 - Slide 34

Convergent Polypeptide Synthesis

Chapter 24 - Slide 35

Solid-Phase Polypeptide Synthesis: (Merrifield Synthesis)

Chapter 24 - Slide 36

Amino Protecting Groups

Amino groups commonly protected as carbamates

Chapter 24 - Slide 37

Carboxyl Protecting Groups

Methyl, ethyl, and benzyl esters

Chapter 24 - Slide 38

Peptide Bond Forming Reaction

Chapter 24 - Slide 39

Last modified 12/26/96

Dr. Abby Parrill
Department of Chemistry
Michigan State University

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