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 this study was to determine the biological activity of four cyclic dipeptides synthesized in this laboratory: cyclo(L-phenylalanyl-L-prolyl), cyclo(L-tyrosyl-L-prolyl), cyclo(L-tryptophanyl-L-prolyl) and cyclo(L-tryptophanyl-L-tryptophanyl). The enhancement or inhibition of calcium channels in ventricular myocytes from rats and delayed-rectifier potassium channels in ventricular myocytes from guinea-pigs were determined by use of the whole-cell patch-clamp technique. The induction of differentiation in HT-29 cells was assessed by assaying for an increase in the expression of alkaline phosphatase. Antibiotic properties against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilus and Streptococcus sp. were determined by use of the Kirby-Bauer disc-diffusion assay. Results from these assays indicate that the cyclic dipeptides have biological activity in both prokaryotes and eukaryotes. Three of the dipeptides block cation channels in ventricular myocytes and all increase the expression of alkaline phosphatase. All the dipeptides have concentration-dependent antibacterial properties. These results suggest that with increased solubility the cyclic dipeptides might have potential as muscle relaxants, anti-tumour compounds and antibiotics.
Milne
P J
PJ
School of Pharmacy, University of Port Elizabeth, Republic of South Africa.
Hunt
A L
AL
Rostoll
K
K
Van Der Walt
J J
JJ
Graz
C J
CJ
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D015220:Calcium Channels / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects
D000900:Anti-Bacterial Agents; D015220:Calcium Channels; D004151:Dipeptides; D010456:Peptides, Cyclic; D015221:Potassium Channels; C118540:cyclo(phenylalanyl-prolyl); C118539:cyclo(tryptophyl-prolyl); C118538:cyclo(tryptophyl-tryptophyl); C118541:cyclo(tyrosyl-prolyl)