Question

What are some of the challenges to working with proteins rather than small chemical compounds?

Answer 1

Proteins are one of the major biomolecules that makes us living organisms and carry out numnerous functions inside living organisms.

Working with smaller chemical compounds is easy. Determination of the structure of a smaller chemical compounds is very simple and we can easily find it by primitive spectroscopic techniques. The synthesis of such compounds is also relatively simple as we need not to construct a larger molecules. Thus, they can be synthesized by the available reagents and combining various known reactions. Dealing with their functionality is also an easy thing.

But proteins are bigger oragnic molecules. They are actually a sequence of amino acids. Determining the structure of a protein involves an initial breakdown of the structure and analysing them. There are various stereochemical aspects in their structure which must be considered. The relative configurations at all the chiral centres must be studied which is very difficult is the protein is bigger (i.e., a polypeptide chain with more amino acids). Complete structural elucidation of a protein requires the extraction of its three-dimensional structure. There are primary, secondary and tertiary structures for a protein. Working with all these structures is very difficult than simply working with smaller molecules.

The synthesis of a specific protein involves step by step addition of the available amino acids according to the available sequence. At each addition there is protection, addition and deprotection. Thus for growing the length of a peptide chain by one amino acid by one amino acid involves a minimum of three steps. Thus, a protein with 10 amino acids involves a minimum of thirty steps in its synthesis. Therefore, with careful preparation of a protein by performing these steps is a challenge and sometimes involves in very low yields.

Studying the functioning of a protein is also a challenging thing as specific active site of the protein is difficult in a large polypeptide chain. The three dimensional structure sometimes changes the properties of the protein.