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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
1. Peptide bonds have double bond character resulting from resonance stabilization
(C-N bond has 40% double bond character) C-N and C-O have partial double bond character
Animation: http://www.mcphu.edu/netbiochem/movies/peptresn.mov
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
- No tendency to protonate
- No significant rotation occurs around the peptide bond itself.
- PEPTIDE BACKBONE is made up of these rigid planar units with limited
rotation around the Cα carbons – N- Cα1 (phi) and the Cα2−C (psi) bonds. These
bonds link the peptide groups in the peptide chain
o Crucial for protein structure
o Rotation can occur at the α−carbons
o However, rotation is limited due to steric hindrance (R groups)
o These limitations limit the shapes that can be assumed by protein chains
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
SUMMARY:
1. Cα, O, C, N and H atoms are planar
2. No rotation around the peptide bond
3. Cα (with R groups) groups are in trans configuration (i.e. H on the
amide Nitrogen is opposite to the Oxygen of the carbonyl)
4. Peptide backbone is rigid
- Peptide = ALDS
- Left Right = N C-terminus (amino to carboxyl termini)
- Want to draw it at pH 5
1) Draw the PEPTIDE BACKBONE fully protonated for as many amino acids as you
have. For convenience, convention and ease, put the R groups down and the
carbonyls up.
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
2. Add in the side chains onto the Cα carbons – the ones that have the CH group –
in order left to right. Draw side chains fully protonated as well.
3. Determine if groups are ionized at the pH that you are interested in.
Go back to fully protonated figure above and remove 2 protons: One from the terminal carboxyl,
and one from the side chain of Asp.
Note: In di, tri, or polypeptides, there is only ONE free amino group (N-terminus) and
ONE free carboxyl group UNLESS present in R groups.
You should be able to write out the full structures of peptides at different pH values.
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
Sketch out starting with fully protonated and remove protons in order until you get the
neutral species. Take the average of the pKa’s surrounding the neutral species.
Net charge at low pH = +3, so have to add 3 equivalents of base to get to net charge zero. 3
equiv. base would completely titrate the α-carboxyl, R-carboxyl, and His imidazole, so pI
would be halfway between pK of imidazole and pK of α-amino group, i.e. (6.0 + 8.3)/2 so pI
= 7.15.
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
Phenylketonuria:
- Genetic deficiency in phenylalanine
hydroxylase, the enzyme that converts
Phe Tyr (autosomal recessive)
- Incidence: PKU appears in about 1 in
10,000 births in Caucasian and East
Asians. Some are higher: Turks are 1 in
2600, Irish are 1 in 4500, and some are
lower - Japanese 1 in 143, 000.
Exceedingly rare in Africans.
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CHM333 LECTURE 8: 9/10/07 FALL 2007 Professor Christine Hrycyna
- If left untreated, severe mental retardation occurs after birth due to accumulation of Phe in
brain – poisons neurons
- Testing of all infants in US and most of
Europe began in mid 1960’s
- Testing occur about 48 to 72 hours after birth
- Treatment: Low Phe diet and blood
monitoring
- In phenylketonurics, Tyr is an essential amino
acid
- Reason for warning label on foods containing
NutraSweet
- One of the most thoroughly tested and studied
food additives the FDA has ever approved – considered safe for the general population
- Aspartame ingestion does produce methanol, formaldehyde and formate, substances that
could be considered toxic, but the levels produced are low.
- No “credible evidence” that there is a link between Aspartame and multiple sclerosis,
systemic lupus, Alzheimer’s disease or vision problems.
- Beware what you read on the internet! Not always factual or credible!
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