Milne P J, Hunt A L, Rostoll K, Van Der Walt J J, Graz C J
School of Pharmacy, University of Port Elizabeth, Republic of South Africa.
J Pharm Pharmacol. 1998 Dec;50(12):1331-7. doi: 10.1111/j.2042-7158.1998.tb03355.x.
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.
环二肽因其结构简单且构象自由度有限，被广泛用作较大肽段的模型。一些环二肽已被证明具有抗病毒、抗菌和抗肿瘤活性。本研究的目的是测定在本实验室合成的四种环二肽的生物活性：环（L-苯丙氨酰-L-脯氨酰）、环（L-酪氨酰-L-脯氨酰）、环（L-色氨酰-L-脯氨酰）和环（L-色氨酰-L-色氨酰）。采用全细胞膜片钳技术测定大鼠心室肌细胞钙通道的增强或抑制以及豚鼠心室肌细胞延迟整流钾通道的变化。通过检测碱性磷酸酶表达的增加来评估HT-29细胞的分化诱导情况。采用Kirby-Bauer纸片扩散法测定对大肠杆菌、铜绿假单胞菌、肺炎克雷伯菌、金黄色葡萄球菌、枯草芽孢杆菌和链球菌属的抗菌特性。这些实验结果表明，环二肽在原核生物和真核生物中均具有生物活性。其中三种二肽可阻断心室肌细胞中的阳离子通道，且均能增加碱性磷酸酶的表达。所有二肽均具有浓度依赖性抗菌特性。这些结果表明，随着溶解度的增加，环二肽可能具有作为肌肉松弛剂、抗肿瘤化合物和抗生素的潜力。
