Pharmacological elements in clinical application of synthetic peptides

The research carried our on the biological properties of synthetic peptides and the possibility of obtaining them in adequate amounts through the reco mbinant DNA technology allows their use as therapeutical agents. Procedures following the synthesis of peptides must be performed in order to verify t heir structure, conformation, immunogenicity and biological activity and to make them suitable for clinical applications. The size of synthetic peptid es together with some modifications such as amidation, acetylation and sulf atation must be taken into consideration as they may have a significant imp act on half-life, stability and biological activity. Endothelial, epithelia l and enzymatic interference which may hinder the absorption of drugs must be evaluated in order to choose the most appropriate route of administratio n. The considerable bioavailability related to the intravenous route, the e ffectiveness of the circulation of the intramuscular route and the possibil ity of reaching: specific targets by the intra-arterial route must also be taken into consideration. There is the possibility of applying transdermal therapeutic systems and transdermal iontophoresis only for peptides of low molecular weight. Among synthetic peptides provided with antianaemic activi ty, erythropoietin, growth factors and interleukin 3 must be mentioned beca use of their effectiveness both in optimal stimulation of myelopoiesis afte r chemotherapy or bone-marrow transplantation and in the treatment of anaem ia occurring during chronic renal failure. Furthermore, interferon alpha wa s shown to be one of the most used synthetic peptides provided with antivir al and antineoplastic activity. Remarkable results have been obtained in th e treatment of chronic hepatitis C, haematological malignancies and some so lid tumours. More recently, interleukin 2 has been tested in the treatment of melanoma and renal cancer, inducing a reasonable proportion of overall r esponse rate. Finally, the antagonist of gonadotropin-releasing-hormone may be regarded as effective agent both in the treatment of prostate cancer an d in the inhibition of luteinizing-hormone surges during controlled ovarian stimulation. Toxic side effects can be related to the administered dose as well as to metabolites derived from bacteria in which peptides have been s ynthesized. (C) 2000 Editions scientifiques et medicales Elsevier SAS.