Biological Activity of Amphiphilic Polymers

Peptides are long, continuous and unbranched chain polymers formed by the polymerisation of amino acid monomers. During the polymerisation process two units are linked together via a peptide bond (-CO-NH-), which is formed by the reaction of a carboxylic group (-COOH) of one amino acid and an amino group (-NHi) of another. Peptides naturally occur in animals and plants, and can also be synthesised in the laboratory. Peptides play a significant role in the prevention of bacterial infections and, to date, more than 5,000 antimicrobial peptides (AMP) have been discovered or synthesised. 

Gad-1 and Gad-2 are rich in histidine which suggests their antimicrobial activities are pH dependent [39-41]. McDonald and co-workers synthesised Gad-1 and Gad -2 under solvent-free conditions and determined their structure-function relationships. They measured the MIC for Gad-1 and Gad-2 against Escherichia coli at pH 5 and pH 7 it was found that the MIC for Gad-1 is 5.1 pM (12.5 pg/ml) at pH 5 and 7 thus, the activities of Gad-1 are not pH dependent. When the same experiments were carried out with Gad-2, it was found that the MIC is 11.5 pM (25 pg/ml) at pH 5 and at pH 7 the MIC is greater than 23.0 pM. It is obvious from the above experiments that Gad-2 is highly pH dependent and showed greater activity at pH 5 than pH 7. 

McDonald and co-workers reported that Gad-1 and Gad-2 exhibited concentration-dependent cytotoxicity against Lewis lung carcinoma (LLC) cells, HEY ovarian cancer cells and PC3 prostate cancer cells. The cytotoxic effect of Gad-1 is greater than Gad-2 [42-47]. Both peptides exhibited considerably higher killing of ovarian and prostate cells under acidic conditions, but Gad-2 showed a significant pH-dependent change in activity with all three carcinoma cell lines [48a]. 

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