Download CHAP Twenty-Five - Foothill College

Armstrong
Foothill College
CHEM 12C
OUTLINE: KLEIN CHAPTER 25:
AMINO ACIDS AND POLYPEPTIDES
1) Amino Acid Structure
A) Stereochemistry
B) Acid/Base properties
C) Zwitterion
D) pI definition and calculations
E) Gel electrophoresis
2) Synthesis of Amino Acids
A) Hell-Volhard-Zelinsky: Carboxylic acid to α-haloacid then SN2 reaction w
excess ammonia
B) Streker Synthesis: Aldehyde with NH4Cl and NaCN
C) Amido Malonate Synthesis: Diethyl acetamidomalonate alkylation, hydrolysis
and decarboxylation
3) Peptides : Primary structure
A) The peptide bond
B) Hindered rotation and 1H NMR
C) Sequencing via Selective Cleavage
i) With aqueous acid at every peptide bond
ii) Edman Degradation: N terminus
iii) DNFB to identify N-terminus
iv) Chymotripsin at C-terminus
v) With cyanogen bromide BrCN at methionine C terminus
vi) With chymotripsin at C end of phe, tyr, trp
vii) With Tripsin at C end of lys, arg
D) Separation and Identification of aa fragments via Gel electrophoresis, Ionexchange chromatography, and Mass Spectrometry
4) Peptide Synthesis
A) Traditional solution synthesis
i) Role of DCC
ii) N-protecting groups: BOC and FMOC
iii) C-protecting groups: PhCH2OH and 1° ROH
B) Merrifield Solid Phase synthesis
LEARNING OUTCOMES:
1) Deduce a polypeptide structure from a series of selective enzyme cleavage
experimental results.
2) Propose the synthesis of a racemic amino acid from an aldehyde or carboxylic
acid.
3) Interpret the 1H NMR of a dipeptide
4) Predict the structure/ proton state of an amino acid at any given pH.
EXAMPLE PROBLEMS:
1)
2) Name and draw the amino acid formed in the following reaction sequence
O
O
H3O+
1. NaOEt
EtO
OEt
2. 1-chloro-2-methylpropane
heat
HN
O
3) Use three letter codes to identify the following polypeptide:
SH
O
O
H
N
H
N
H2N
N
H
O
OH
O
OH