Pharmacological elements in clinical application of synthetic peptides.
The research carried out on the biological properties of synthetic peptides and the possibility of obtaining them in adequate amounts through the recombinant DNA technology allows their use as therapeutical agents. Procedures following the synthesis of peptides must be performed in order to verify their structure, conformation, immunogenicity and biological activity and to make them suitable for clinical applications. The size of synthetic peptides together with some modifications such as amidation, acetylation and sulfatation must be taken into consideration as they may have a significant impact on half-life, stability and biological activity. Endothelial, epithelial and enzymatic interference which may hinder the absorption of drugs must be evaluated in order to choose the most appropriate route of administration. The considerable bioavailability related to the intravenous route, the effectiveness of the circulation of the intramuscular route and the possibility 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 activity, erythropoietin, growth factors and interleukin 3 must be mentioned because of their effectiveness both in optimal stimulation of melopoiesis after chemotherapy or bone-marrow transplantation and in the treatment of anaemia occurring during chronic renal failure. Furthermore, interferon alpha was shown to be one of the most used synthetic peptides provided with antiviral and antineoplastic activity. Remarkable results have been obtained in the treatment of chronic hepatitis C, haematological malignancies and some solid tumours. More recently, interleukin 2 has been tested in the treatment of melanoma and renal cancer, inducing a reasonable proportion of overall response rate. Finally, the antagonist of gonadotropin-releasing-hormone may be regarded as effective agent both in the treatment of prostate cancer and 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 synthesized.
Lauta
V M
VM
University of Bari Medical School, Department of Biomedical Sciences and Human Oncology, Italy. dimoclin@cimedoc.uniba.it
D004333:Drug Administration Routes; D006801:Humans; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use
D016898:Interferon-alpha; D010455:Peptides; D011994:Recombinant Proteins