How do amino acids combine to form proteins

Free courses. All content. Course content. About this free course 8 hours study. Level 1: Introductory. Course rewards. Free statement of participation on completion of these courses.

Create your free OpenLearn profile. Course content Course content. Nutrition: Proteins Start this free course now. A model of hemoglobin was shown above, and may also be examined by clicking the image on the left.

In animals, hemoglobin transports oxygen from the lungs or gills to the rest of the body, where it releases the oxygen for cell use. Hemoglobin's oxygen-binding capacity is decreased in the presence of carbon monoxide because both gases compete for the same binding sites on hemoglobin.

The binding affinity of hemoglobin for CO is times greater than its affinity for oxygen. When hemoglobin combines with CO, it forms a very bright red compound called carboxyhemoglobin, which may cause the skin of CO poisoning victims to appear pink in death.

Similarly, hemoglobin has a competitive binding affinity for cyanide, sulfur monoxide, nitrogen dioxide and sulfides including hydrogen sulfide.

All of these bind to the heme iron without changing its oxidation state, causing grave toxicity. Insulin is a peptide hormone composed of 51 amino acids, with a molecular weight of Da.

Insulin has a strong effect on metabolism and other body functions, causing cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle. Insulin is formed in the islets of Langerhans in the pancreas. The molecular structure of insulin varies slightly between species of animals. Porcine pig insulin is especially close to the human version.

Insulin molecules have a tendency to form dimers in solution due to hydrogen-bonding between the C-termini of B chains. In the presence of zinc ions, insulin dimers associate into hexamers. Insulin is stored in the body as a hexamer, whereas the active form is the monomer. These interactions have important clinical ramifications.

Monomers and dimers readily diffuse into blood; hexamers diffuse poorly. By clicking the image on the far left, a model of the insulin monomer will be displayed. A model of the hexamer will be shown by clicking its image. The virus makes certain proteins that need to be cleaved or cut, in order to transform into functional proteins that enable the virus to infect new cells. HIV-1 protease cleaves the nascent proteins into their functional form.

The enzyme is composed of two symmetrically related subunits, shown here in cartoon backbone representation to highlight the secondary structure. Each subunit consists of the same small chain of 99 amino acids, which come together in such as way as to form a tunnel where they meet.

The protein to be cleaved sits in this tunnel, which houses the active site of the enzyme. Two Asp-Thr-Gly catalytic triads, one on each chain, compose the active site. The two Asp's act as the main catalytic agents, and together with a water molecule cleave the protein chain bound in the tunnel.

Such drugs function as inhibitors, binding to the active site by mimicking the tetrahedral intermediate of its substrate, thus disabling the enzyme. The structure of one such inhibitor, BEA, will be displayed on the left by clicking here. Tropomyosin The following animation shows a segment of the fibrous protein tropomyosin, a common muscle regulator. The peptide chains are largely alpha-helices. These are wrapped in superhelix pairs, which are then aligned in a parallel array.

In order to synthesize a peptide from its component amino acids, two obstacles must be overcome. The first of these is statistical in nature, and is illustrated by considering the dipeptide Ala-Gly as a proposed target. If we ignore the chemistry involved, a mixture of equal molar amounts of alanine and glycine would generate four different dipeptides. In the case of tripeptides, the number of possible products from these two amino acids rises to eight.

Clearly, some kind of selectivity must be exercised if complex mixtures are to be avoided. From the perspective of an organic chemist, peptide synthesis requires selective acylation of a free amine. To accomplish the desired amide bond formation, we must first deactivate all extraneous amine functions so they do not compete for the acylation reagent.

Then we must selectively activate the designated carboxyl function so that it will acylate the one remaining free amine. Fortunately, chemical reactions that permit us to accomplish these selections are well known. First, the basicity and nucleophilicity of amines are substantially reduced by amide formation. Second, acyl halide or anhydride-like activation of a specific carboxyl reactant must occur as a prelude to peptide amide bond formation.

This is possible, provided competing reactions involving other carboxyl functions that might be present are precluded by preliminary ester formation. Remember, esters are weaker acylating reagents than either anhydrides or acyl halides, as noted earlier. Finally, dicyclohexylcarbodiimide DCC effects the dehydration of a carboxylic acid and amine mixture to the corresponding amide under relatively mild conditions.

The structure of this reagent and the mechanism of its action have been described. Its application to peptide synthesis will become apparent in the following discussion. The strategy for peptide synthesis, as outlined here, should now be apparent. The following example shows a selective synthesis of the dipeptide Ala-Gly. An important issue remains to be addressed. Since the N-protective group is an amide, removal of this function might require conditions that would also cleave the just formed peptide bond.

Furthermore, the harsh conditions often required for amide hydrolysis might cause extensive racemization of the amino acids in the resulting peptide. This problem strikes at the heart of our strategy, so it is important to give careful thought to the design of specific N-protective groups. In particular, three qualities are desired:.

A number of protective groups that satisfy these conditions have been devised; and two of the most widely used, carbobenzoxy Cbz and t-butoxycarbonyl BOC or t-BOC , are described here.

The reagents for introducing these N-protective groups are the acyl chlorides or anhydrides shown in the left portion of the above diagram. Reaction with a free amine function of an amino acid occurs rapidly to give the "protected" amino acid derivative shown in the center. This can then be used to form a peptide amide bond to a second amino acid.

Once the desired peptide bond is created the protective group can be removed under relatively mild non-hydrolytic conditions. Equations showing the protective group removal will be displayed above by clicking on the diagram.

Cleavage of the reactive benzyl or tert-butyl groups generates a common carbamic acid intermediate HOCO-NHR which spontaneously loses carbon dioxide, giving the corresponding amine.

If the methyl ester at the C-terminus is left in place, this sequence of reactions may be repeated, using a different N-protected amino acid as the acylating reagent. Removal of the protective groups would then yield a specific tripeptide, determined by the nature of the reactants and order of the reactions. The synthesis of a peptide of significant length e. To facilitate the tedious and time consuming purifications, and reduce the material losses that occur in handling, a clever modification of this strategy has been developed.

This procedure, known as the Merrifield Synthesis after its inventor R. Bruce Merrifield , involves attaching the C-terminus of the peptide chain to a polymeric solid, usually having the form of very small beads.

Separation and purification is simply accomplished by filtering and washing the beads with appropriate solvents. The reagents for the next peptide bond addition are then added, and the purification steps repeated. The entire process can be automated, and peptide synthesis machines based on the Merrifield approach are commercially available.

A series of equations illustrating the Merrifield synthesis may be viewed by clicking on the following diagram. The actual order of the amino acids in the protein is called its primary structure and is determined by DNA. The order of deoxyribonucleotide bases in a gene determines the amino acid sequence of a particular protein. The secondary structure of the protein is due to hydrogen bonds that form between the oxygen atom of one amino acid and the nitrogen atom of another and gives the protein or polypeptide the two-dimensional form of an alpha-helix or a beta-pleated sheet.

Other interactions between R groups of amino acids such as hydrogen bonds, ionic bonds, covalent bonds, and hydrophobic interactions also contribute to the tertiary structure. In some proteins, such as antibody molecules, several polypeptides may bond together to form a quaternary structure. Contributors and Attributions Dr. A peptides is a molecule composed of two or more amino acids. The bond that holds together the two amino acids is a peptide bond, or a covalent chemical bond between two compounds in this case, two amino acids.

It occurs when the carboxylic group of one molecule reacts with the amino group of the other molecule, linking the two molecules and releasing a water molecule. Long chain polypeptides can be formed by linking many amino acids to each other via peptide bonds. The amide bond can only be broken by amide hydrolysis, where the bonds are cleaved with the addition of a water molecule. The peptide bonds of proteins are metastable, and will break spontaneously in a slow process.

Living organisms have enzymes which are capable of both forming and breaking peptide bonds. The Amide Bond : Peptide bonds are amide bonds, characterized by the presence of a carbonyl group attached to an amine. The amide group has three resonance forms, which confer important properties. The peptide bond is uncharged at normal pH values, but the double bonded character from the resonance structure creates a dipole, which can line up in secondary structures.

The partial double bond character can be strengthened or weakened by modifications that favor one another, allowing some flexibility for the presence of the peptide group in varying conditions. The extra stabilization makes the peptide bond relatively stable and unreactive. However, peptide bonds can undergo chemical reactions, typically through an attack of the electronegative atom on the carbonyl carbon, resulting in the formation of a tetrahedral intermediate.

Privacy Policy. Skip to main content. Search for:.