Affinity chromatography using protein A from Staphylococcus aureus as the ligand 
has been widely used for the isolation of immunoglobulin G (IgG) from various 
species. Since ligand leakage from the affinity support can occur, time 
consuming analytical controls are required to detect the presence of 
contaminants associated with the isolated IgG prior to its use for therapeutic 
purpose in humans. Besides, protein A is an expensive bacterial product, whose 
isolation involves complex and labor intensive procedures. Combinatorial 
chemistry enables the synthesis of a wide variety of ligands within a short 
period of time. Therefore, chemically defined, stable and inexpensive ligands, 
which can mimic the action of protein A, have been developed to isolate 
immunoglobulins. Two different types of ligands, synthesized following the 
techniques of combinatorial chemistry, have been used to isolate 
immunoglobulins. One of them is a synthetic peptide (TG 19318) comprising four 
identical tripeptide chains linked to a central polylysine core. Immobilized TG 
19318 has been used to isolate polyclonal and monoclonal antibodies of different 
classes (IgG, IgM, IgA, IgE) from different sources (serum, ascities and cell 
supernatants) and species. The ligand has a binding capacity that can reach upto 
25mg IgG/mL of the support. It is stable when treated with sanitation agents 
such as ethanol and 0.1 M sodium hydroxide. Computer-aided molecular design and 
combinatorial chemistry have been used to develop an IgG binding affinity ligand 
(22/8), which consists of two organic aromatic amines (3-aminophenol and 
4-amino-1-napthol) linked to a scaffold of cyanuric chloride (triazine). Ligand 
22/8 displayed wider specificity than protein A, as it isolated IgG from a 
number of species, the order of adsorption being human> chicken > cow > rabbit > 
pig > horse > rat > goat > sheep > mouse. It showed an apparent binding capacity 
of 51.9 mg IgG/g moist gel and can isolate human IgG from plasma in 60% yield 
with a purity of 92%. The ligand is stable, as it withstood incubation in 1M 
NaOH for a week without loss of binding capacity for IgG. These findings suggest 
that synthetic affinity ligands, which are inexpensive, stable and specific can 
facilitate the purification of immunoglobulins in a cost-effective manner.