Download Chem331 Lect 5 Amino acids peptides

Amino Acids
20 common amino acids there are others found naturally but much less frequently
Common structure for amino acid
COOH, -NH2, H and R functional groups all attached to the a carbon
Ionization of amino acids
Amino Acid Basics
pKa of the a amino and a carboxyl differ based on R group and microenvironment. See pg 79 and figures.
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The average is about 2.1 for the alpha carboxyl and 9.7 for the alpha amino groups
Amino acids are zwitterions - a molecule with both a pos and neg charge
All naturally occurring amino acids are optically active isomers, except glycine. L amino acids
R-groups determine the functionality of the amino acids.
All amino acids can be based on one of three basic groups, non-polar, uncharged polar and charged polar.
Also are classified based on hydrophobicity, reactivity, acidic and basic nature, relative size of the side groups
The 20 Common Amino Acids
You should know names, structures, pKa values for carboxyl and amino terminus, approximate pKa for ionizable
groups, 3-letter designation (not single letter).
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Non-polar amino acids
Polar, uncharged amino acids
Hydrophobic/hydrophilic
Large steric bulky or small
Common reactions of amino acids
Unique features of unusual amino acids (Pro, Met, Cys…)
Acidic amino acids
Basic amino acids
Non-Polar Amino Acids
Aliphatic, inert and non polar. These are very hydrophobic amino acids with various sized side groups.
Non-Polar Amino Acids
Aliphatic, inert and non polar. These are very hydrophobic amino acids with various sized side groups.
Non-Polar Amino Acids
Proline is the only aa where the alpha amino group is tied up in a ring structure. This amino acid is only slightly
hydrophobic.
The ring structure decreases the flexibility of the peptide backbone.
Polar Uncharged Amino Acids
Hydrophilic (except Gly). Which of the side groups have potential for being involved in H bonding and salt
bridges?
Polar Uncharged Amino Acids
All are hydrophilic. Which of the side groups have potential for being involved in H bonding and salt bridges?
Acidic Amino Acids
All are hydrophilic. Which of the side groups have potential for being involved in H bonding and salt bridges?
Basic Amino Acids
Less Common Amino Acids
Amino acids which rarely occur in proteins but are important for function
These amino acids are not synthesized by ribosomal processes; most typically arise from post-translational
modifications to the protein, which are catalyzed by specific enzymes.
You are not responsible for knowing these amino acids, but should be aware they exist
SPECIAL CASES – CYSTEINE
Hydrophilic amino acid contains sulfur. Cysteine is very reactive and involved in the structure of the protein. Involved in disulfide bonds when oxidized.
Side groups with -OH
Ser, Thr and Tyr
-Only slightly hydrophilic.
-The OH is only ionizable under very basic conditions.
-The OH groups are very reactive and are phosphorylated similar to tyrosine.
Phenylalanine, tyrosine and tryptophan All are aromatic rings. Pi bonds / e- clouds
create a very hydrophobic aa. Phenylalanine is very low in relative
concentrations.
Trp and Tyr absorb at 280 nm. Peptide backbone absorb at 260 nm.
These aa contain phenyl and indol rings.
Biologically important aa
Additional Reactions of Amino Acids
Carboxyl groups form amides & esters
Amino (e) groups of lysine forms Schiff bases
Side chains show unique reactivities
• Cys residues can form disulfides and can be easily alkylated
• Few reactions are specific to a single kind of side chain
More titrations
When the amino acid is has a 0 net charge that is considered the isoelectric point. For amino acids with side
groups that contain an ionizable moiety it is the average of the two pKa that are charged when the net charge is
zero.
Isoelectric Points
If the side group is not ionizable, then the pI is the average of the C and N groups pKa
Calculations of pI for a compound with more than two dissociable groups carries more possibility for error
First write out all possible ionic structures for a compound in order that they occur starting with the most basic to
the most acidic
Next, identify the isoionic, zwiterionic or neutral representation
The pI is the pH at the midpoint between the pK values on either side of the isoionic species
What about peptides or proteins?
“Peptides”
Peptide formation is the creation of an amide bond between the carboxyl group of one amino acid and the
amino group of another amino acid.
Short polymers of amino acids
Each unit is called a residue
2 residues - dipeptide
3 residues - tripeptide
12-20 residues - oligopeptide
many - polypeptide
Each amino acid is called a residue
Addition of acid or base hydrolyzes the peptide bond and adds water back across the peptide bond.
The amino (N) terminal is written on the left and the carboxyl (C) terminal is on the right.
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Peptide Bond
Rx of bond formation costs energy (ATP) but degradation of proteins is thermodynamically
favorable. (entropy)
C-N bond shorter than normal and more like double bond
This results in rigid planar, non-rotating links between aa
Size of peptides and proteins are described in Daltons
1 atomic unit = 1 dalton ; MW = Dalton / kd; Mr=molecular weight
Peptide Bond
is usually found in the trans conformation
has partial (40%) double bond character
N partially positive; O partially negative
has a length of about 0.133 nm - shorter than a typical single bond but longer than a double bond
Due to the double-bond character of the peptide bond, the six atoms of the peptide bond group define a
plane – the amide plane
The Peptide Bond
The peptide bond has partial double bond character. One of the postulated resonance forms is shown here.
Many peptides have important biological activities
Biologically important peptides
Insulin –
Short peptide produced as a pre-pro-peptide. The initial peptide is much longer and
is modified twice, each time a set of peptide bonds are hydrolyzed. The final
shortened version is active. There are two subunits, held together by a disulfide
bond.
Bioactive Peptides
Oxytocin and Vasopressin
– Start as long precursors in hypothalamus- whose final form is 9 aa
– differ by 2 residues
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oxytocin - uterine contraction during childbirth and milk production during lactation
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vasopressin - alters blood pressure by forcing kidney to retain water, increasing the
volume of blood
Met-enkephalin (opioid peptides)
» Naturally produced peptides, bind to receptors, and reduce pain cause pleasure.
Morphine like
Substance P
» Opposite effect from opioids
» Stimulates perception of pain (protective mechanism)
“Protein” One or more polypeptide chains
One polypeptide chain - a monomeric protein
More than one - multimeric protein
Homomultimer - one kind of chain
Heteromultimer - two or more different chains
Hemoglobin, for example, is a heterotetramer
It has two alpha chains and two beta chains
Proteins - Large and Small
Insulin - A chain of 21 residues, B chain of 30 residues -total mol. wt. of 5,733
Glutamine synthetase - 12 subunits of 468 residues each - total mol. wt. of 600,000
α−Connectin (a muscle protein) - MW 2.8 million
β−Connectin - MW of 2.1 million, with a length of 1000 nm - it can stretch to 3000 nm
The Sequence of Amino Acids in a Protein
Is a unique characteristic of every protein
Is encoded by the nucleotide sequence of DNA
Is thus a form of genetic information
Is read from the amino terminus to the carboxyl terminus