Lecture 3: Macromolecules: Their Chemistry and Biology 9/5/01

Macromolecules: Giant Polymers

Types of biological macromolecules: proteins, carbohydrates, lipids, and nucleic acids. Building blocks: Table 3.1


Some types of macromolecules contain many different kinds of monomers.


Some contain the same simple units, repeated many times.


High Interest:

Structure Determination -> function

Establish function through genetic mutants; change structure -> change in function


Structure Prediction


Rational Drug Design: vs Irrational Drug Design

Irrational (previous norm!) make lots of random compounds, test them using a technique called High Throughput Screening

Rational new model evaluate shape of active site surface, find compounds that will have a shape that blocks site


Differences between monomer units vs polymers: entropy.

Synthesis: Condensation Reactions

Macromolecules are made from smaller monomers by removing an OH from one monomer and an H from another monomer to link them together; water is given off as a result. (See Figure 3.2.) Condensation or dehydration (loss of water) reaction.


Energy must be added to make or break a polymer; bonding favorable


The reverse reaction, breaking polymers back into monomers, is a hydrolysis reaction (hydro means water; lysis, break).


A hydrolysis reaction is one in which water is added and reacts with the bond that links the units together.


It takes special proteins, called enzymes, to make polymers from monomers. Protein synthesis occurs within the ribosome: the active enzyme here is a ribozyme [strands of RNA acting as an enzyme}


Most hydrolysis in biological systems is also performed by enzymes, although a strong acid or base solution can hydrolyze many types of polymers.

In people, stomach acid hydrolyzes some of the linkages found in the polymers we eat.

Proteins: Polymers of Amino Acids

Drawing of a condensation rxn: 2 amino acids -> polypeptide. (Fig 3.2: resonance of single to double bond structure helps stabilize the peptide bond, CONH


Proteins called enzymes are particularly important in biological systems. Enzymes increase the rates of chemical reactions in cells. This function is known as catalysis.


Enzymes are highly specific; in general, each enzyme catalyzes only one chemical reaction.


Proteins range in size from a few amino acids to thousands.


Some proteins are composed of a single chain of amino acids, called a polypeptide.


Other proteins have more than one polypeptide chain. [Quaternary structure!]

Folding is crucial to the function of a protein. Folding is influenced largely by the sequence of amino acids. The final folded structure is the Tertiary structure.


Each different type of protein has a characteristic amino acid composition and order. [Primary structure!]


Proteins are composed of amino acids

Differences in amino acids come from the side chains, or the R groups, found attached to the same carbon as the amino group. (See Table 3.2A-D.)


The 20 common amino acids vary widely in properties


All but one have four different groups that are attached to the a carbon.

A hydrogen atom, an amino group, and a carboxyl group are bonded to the a carbon of all the different amino acids.


The fourth group, the R group, is what makes one type of amino acid different from another.


Glycine has H as its R group and is, therefore, the only amino acid that has three rather than four groups attached to the a carbon.


Carbons with four different groups attached can exist in different stereoisomeric (handedness) forms. All amino acids do, except for glycine.


Amino acids can be classified based on the characteristics of their R groups.

Five of the 20 amino acids form ions in solution depending on pH [charged R groups].


Four of the 20 have polar side chains [polar R groups].


Eight have nonpolar R groups [hydrophobic R groups].


Three amino acids, cysteine, glycine, and proline, have some special properties.

Cysteine has a terminal sulfhydryl (SH) group which often forms a disulfide (SS) bridge with another cysteine. (See Figure 3.3.)


Glycine has a hydrogen atom as the side chain. This group is small enough to fit into small spaces and tight corners when the protein folds.


Proline has a modified amino group that forms a covalent bond with the R group.

Proline's ring limits rotation of the a carbons bond.


Proline is often found at bends and loops of proteins.


Peptide linkages covalently bond amino acids together

Proteins are synthesized by condensation reactions between the amino group of one amino acid and the carboxyl group of another. This forms a peptide linkage. (See Figure 3.4.) See Cechs article, The Ribosome is a Ribozyme.


Proteins are also called polypeptides. A dipeptide is two amino acids long; a tripeptide, three; oligo, a bunch. A polypeptide is multiple amino acids long.


The first amino acid of a peptide is called the N-terminus amino acid because the amino group is free, or unbound.


The last is called the C-terminus amino acid and has a free carboxyl group.


The CN peptide linkage forms a partial double bond, which is a single covalent and polar attraction.


This bond limits folding and restricts the ability of the adjacent atoms to rotate.


Within the central axis of the protein, there is an asymmetry of charge favoring a tendency toward hydrogen bonding. (Oxygen is partially negative and nitrogen is slightly positive.)


The primary structure of the protein is its amino acid sequence.

There are four levels of protein structure: primary, secondary, tertiary, and quaternary. (See Figure 3.5.)


The precise sequence of amino acids is called its primary structure.


The peptide backbone is repeating units of atoms: NCCNCC

In the figure, the portion on the left is the N terminus; on the right is the C terminus.


The protein is synthesized starting from the N terminus and adding to the C terminus.


Many proteins have now been sequenced.

The two conventions for representing the sequence are three-letter and one-letter systems. (See Table 3.2.)


In the three-letter system, methionine is Met; in the one-letter system, it is M.


Amazing numbers of different proteins are possible. N20


The secondary structure of a protein requires hydrogen bonding


Secondary structure is the shape regions of the peptide take on as a folded polymer.


This shape is influenced primarily by the amino acid sequence (the primary structure).


There are two common secondary structures.

One is the a helix, a right-handed coil. (See Figure 3.5b.)

The peptide backbone takes on the helical shape due to hydrogen bonds.


The R groups point away from the peptide backbone.


Large R groups tend to prevent the creation of this structure.


Insoluble fibrous structural proteins have a-helical secondary structures. Examples are the proteins found in hair, feathers, and hooves, called keratins.


Hair stretches because only hydrogen bonds, not covalent bonds, are broken when it is pulled.


Another common secondary structure is b pleated sheets.

These form from peptide regions that lie parallel to each other. (See Figure 3.5c.)


Sometimes the parallel regions are in the same peptide.


Sometimes the parallel regions are from different peptide strands.


This sheet-like structure is stabilized by hydrogen bonds between NH groups on one chain with the C=O group on the other.


Spider silk is made of b pleated sheets from separate peptides. Despite the weakness of the hydrogen bonds, together they tend to be additive; therefore, substances like spider silk can be remarkably strong.

The tertiary structure of a protein is formed by bending and folding


Tertiary structure is the three-dimensional shape of the completed polypeptide. (See Figure 3.5d.)

Lysozyme: Fig 3.6: compare with Hen.lysozyme.1PBX.prt


The primary determinant of the tertiary structure is the interaction between R groups, which is determined by the proteins primary structure.


Other factors are

The nature and location of secondary structures


The location of disulfide bridges, which form between cysteine residues


Hydrophobic side chain aggregation and van der Waals forces, which help stabilize them


The ionic interactions, the positive and negative charges deep in the protein away from water

The quaternary structure of a protein consists of subunits


Some proteins are composed of subunits, which are separate peptide chains that associate together to create the functional protein. (See Figure 3.5e.)


This dimension is called the quaternary structure, and it adds to the 3-D shape of the finished protein.


Quaternary structure results from the ways in which multiple polypeptide subunits bind together and interact.


Hemoglobin is an example of such a protein; it has four subunits, 2 alpha units and 2 beta units. (See Figure 3.7.)

Protein shapes are sensitive to the environment


Changes in temperature, pH, salt concentrations, and oxidation or reduction conditions can change the shape of proteins. This process is called denaturation. (See Figure 3.9.)


Often denaturation is irreversible, like the boiling of egg white.


Some chemically induced changes are reversed by removal of the chemical condition that caused them.


A few proteins, like ribonuclease, resist denaturation; they can be boiled for days and retain activity once cooled.