Biochemistry I Fall Term, 2000

Lecture 5: Peptides

Assigned reading in Campbell: Chapter 3.4-3.5.

Self-guided tour of the amino acids (and view a few peptides):
http://www.bio.cmu.edu/courses/03231/BBlocks/AAVFrameset.htm

3.4 The Peptide Bond

Amino acids are connected together by the formation of a peptide bond (an example of a condensation reaction):

Proteins are linear polymers (polypeptides) that have properties derived from the properties of the amino acids ("emergent properties"). Proteins fold from an extended chain into compact structures. In doing so, a number of amino acids become buried within the core. Some crosslinking can also occur, usually through disulfide bond formation between Cys residues. In simple terms, a folded protein can be described as a sphere with a nonpolar core and a charged surface (i.e. an "oil drop with a polar coat", in a phrase coined by I. Kauzman).

Five Important Features of the Peptide Bond

1. The resonance structures that can be drawn for the peptide bond (Campbell, Fig. 3.9) show that the C-N bond has double bond character. The double bond character of peptides and other amides was deduced by Linus Pauling and coworkers, based on their structure determinations of model compounds. Specifically, the bond length measurements showed that the C=O and C-N bonds were both partial double bonds.
2. The planarity of the peptide was another feature found from the early structure determinations. All four of the atoms boxed in the above figure lie in a plane.
3. The above figure also shows the peptide bond in its highly preferred trans configuration. Rotation of 180° about the C-N bond would produce the cis configuration, but this is rarely observed in proteins.
4. Rotation can and does occur about the two single bonds on either side of the a-carbon.
   

   In the above figure of an octapeptide, these bonds are labelled between residues 1 and 2:

   F (Phi), the bond between N and C_a

   Y (Psi), the bond between C_a and C.

   As drawn, the figure is said to be in the "extended chain conformation", i.e. the peptide bonds lie in the plane and both Y and F = 180°. These two torsion angles correspond to the angles between the adjacent peptide planes and are also called dihedral angles.
   The regular repeating secondary structures of proteins (a-helix and b-sheet) have characteristic values of the Y and F dihedral angles.

   Peptides and polypeptides are numbered from the amino-terminal (N-term) to the carboxy-terminal (C-term) residue. Protein sequences are written left to right from the N- to the C-terminus.

5. The stability of peptide bonds in aqueous solution at pH 7 can be viewed in two ways:

   Thermodynamic: the equilibrium constant for hydrolysis of a peptide bond (the reverse of the condensation reaction shown above) favors hydrolysis by a factor of 10³ to 10⁴. Thus, the peptide bond is unstable with respect to its hydrolysis products.

   Kinetic: the rate of peptide bond hydrolysis under physiological conditions is very slow; the half-time for the reaction can be years. Thus, the peptide bond is stable when considered on a physiological time scale.

   Thermodynamic instabilty and kinetic stability are properties of all biological polymers, i.e. proteins, DNA, RNA, and polysaccharides. These two features figure prominently in the regulation of macromolecular metabolism, topics to be considered later in the course.

3.5 Some Small Peptides of Physiological Interest

The peptides described by Campbell in this section are only a small fraction of known bio-active peptides. But the examples selected are representative and the description is excellent.
Another description with an emphasis on biodiversity topics and an account of the discovery of the magainin peptide is at: Frogs Legs and Parasitic Tales. (See the section, "An unexpected natural shield" on this page.)

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