Protein Recognition by Synthetic Receptors
Proteins are macromolecules made up of one or more chains of amino acids (polypeptide) and each amino acid in a polypeptide chain links by peptide bond. Major biochemical functions of protein include catalysis (enzymes), molecular switches and structural components of cells and organisms. Each organism has a unique amino acid sequence in their protein that is encoded in their genes. Proteins have four levels of structure.
Twenty, different types of amino acids are present and these amino acids form more than 10000 proteins in human body. The sequence of the different amino acids in a polypeptide chain is known as primary structure.
This can take the form of α-helix or β-sheets. Hydrogen bonding between -N-H and -C=O groups holds together the secondary structure of protein. In nature most abundant secondary structure is α-helix (over 30%)5. α-helix contains 3.4 amino acid residues in one turn. Side chains of i, i+4, i+7 and i+11 residues are at the same face and form intra molecular H-bond. This bond stabilizes the α-helix structure.
β-sheets form inter molecular H-bond with adjacent peptide in either parallel or anti parallel format. Side chains are at perpendicular to the plane of the hydrogen bonding axis.
This determines the overall three dimensional shape of a single polypeptide chain molecule and can be stabilized by hydrogen bonds, disulphide bonds.
Association of more than one poly peptide chains constitutes the quaternary structure.
Proteins play a vital role in most of the biologically important processes for example molecular recognition and catalysis. Molecular recognition is especially important in the functioning of enzymes. To study a specific enzyme activity one must first recognizes the substrate, the intermediate transition state and its chemical transformation in the body. These impressive results in nature form an inspiration for chemist to mimic natural functions and modify them to unnatural situations. Supra molecular systems provide new models for molecular recognition processes.
Protein – protein interactions (PPI) are considered as un druggable in ancient time but this challenge was overcome by the synthesize of small molecules. The ability to control PPIs will develop new molecular therapeutics and will establish novel approaches for medical diagnostics for diseases.
Folded protein conformation creates two surfaces and those are
- Solvent exposed surface here interactions occurs on the surface of protein. Functional groups are divergent in nature and the binding molecules require the involvement of large surface areas and different functionalities. Therefore artificially designed molecules to inhibit biologically active solvent exposed surface sites of proteins are rare.
- Solvent excluded surface here the interactions occurs inside protein. For example enzyme active sites are...