Graz M, Hunt A, Jamie H, Grant G, Milne P
Cyclic Peptide Research Unit, University of Port Elizabeth, South Africa.
Pharmazie. 1999 Oct;54(10):772-5.
Cyclic dipeptides are products of rational drug design, which may exhibit both antimicrobial and antitumor properties. The aim of this study was to investigate both the antimicrobial effects of the cyclic dipeptides cyclo(L-phenylalanyl-L-prolyl), cyclo(L-tyrosyl-L-prolyl), cyclo(L-tryptophanyl-L-prolyl) and cyclo(L-tryptophanyl-L-tryptophanyl) and the effects of these cyclic dipeptides on the gastrointestinal epithelium in vitro. Furthermore, a relevant solvent for the possible pharmaceutical application of the products was sought concurrently. The antimicrobial effect of the cyclic dipeptides was assayed using the Kirby-Bauer disc diffusion assay against Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis, Streptococcus pneumoniae, Candida albicans, Aspergillus niger and Penicillium notatum. The effect of the cyclic dipeptides on the gastrointestinal epithelium was assessed by changes in alkaline phosphatase expression of HT-29 cells. Cyclo(Pro-Trp) and cyclo(Phe-Pro) show broad spectrum antibacterial properties and cyclo(Trp-Pro) and cyclo(Trp-Trp) show broad spectrum antifungal properties. The maturation of the gastrointestinal cells was enhanced by cyclo(Phe-Pro), cyclo(Tyr-Pro), cyclo(Trp-Trp) and cyclo(Trp-Pro). The activity of these cyclic dipeptides thus indicates potential application of these compounds as pharmacological agents.
环二肽是合理药物设计的产物，可能具有抗菌和抗肿瘤特性。本研究的目的是研究环（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）这几种环二肽的抗菌作用以及它们在体外对胃肠道上皮细胞的影响。此外，还同时寻找了这些产物可能用于制药的相关溶剂。采用Kirby-Bauer纸片扩散法检测环二肽对大肠杆菌、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、肺炎链球菌、白色念珠菌、黑曲霉和青霉的抗菌作用。通过HT-29细胞碱性磷酸酶表达的变化来评估环二肽对胃肠道上皮细胞的影响。环（脯氨酸-色氨酸）和环（苯丙氨酸-脯氨酸）具有广谱抗菌特性，环（色氨酸-脯氨酸）和环（色氨酸-色氨酸）具有广谱抗真菌特性。环（苯丙氨酸-脯氨酸）、环（酪氨酸-脯氨酸）、环（色氨酸-色氨酸）和环（色氨酸-脯氨酸）可增强胃肠道细胞的成熟。因此，这些环二肽的活性表明这些化合物作为药物制剂具有潜在的应用价值。
