The biological activity of selected cyclic dipeptides

Cyclic dipeptides are widely used as models for larger peptides because of their simplicity and limited conformational freedom. Some cyclic dipeptides have been shown to be antiviral, antibiotic and anti-tumour. The aim of th is study was to determine the biological activity of four cyclic dipeptides synthesized in this lab oratory: cyclo(L-phenylalanyl-L-prolyl), cyclo(L-t yrosyl-L-prolyl), cyclo(L-tryptophanyl-L-prolyl) and cyclo(L-tryptophanyl-L -tryptophanyl). The enhancement or inhibition of calcium channels in ventricular myocytes f rom rats and delayed-rectifier potassium channels in ventricular myocytes f rom guinea-pigs were determined by use of the whole-cell patch-clamp techni que. The induction of differentiation in HT-29 cells was assessed by assayi ng for an increase in the expression of alkaline phosphatase. Antibiotic pr operties against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneum oniae, Staphylococcus aureus, Bacillus subtilus and Streptococcus sp. were determined by use of the Kirby-Bauer disc-diffusion assay. Results from,the se assays indicate that the cyclic dipeptides have biological activity in b oth prokaryotes and eukaryotes. Three of the dipeptides block cation channe ls in ventricular myocytes and all increase the expression of alkaline phos phatase. All the dipeptides have concentration-dependent antibacterial prop erties. These results suggest that with increased solubility the cyclic dipeptides might have potential as muscle relaxants, anti-tumour compounds and antibio tics.