Effects of Modifications on the Immunosuppressive Properties of Cyclolinopeptide A and Its Analogs in Animal Experimental Models

The consequences of manipulations in structure and amino acid composition of native cyclolinopeptide A (CLA) from linen seeds, and its linear precursor on their biological activities and mechanisms of action, are reviewed. The modifications included truncation of the peptide chain, replacement of amino acid residues with proteinogenic or non-proteinogenic ones, modifications of peptide bond, and others. The studies revealed changes in the immunosuppressive potency of these analogs investigated in a number of in vitro and in vivo experimental models, predominantly in rodents, as well as differences in their postulated mechanism of action. The modified peptides were compared with cyclosporine A and parent CLA. Some of the synthesized and investigated peptides show potential therapeutic usefulness.

Effects of Modifications on the Immunosuppressive Properties of Cyclolinopeptide A and its Analogs in Animal Experimental Models

The consequences of manipulations in structure and amino acid composition of native cyclolinopeptide A (CLA) from linen seeds and its linear precursor on their biological activities and mechanisms of action are reviewed. The modifications included truncation of the peptide chain, replacement of amino acid residues with proteinogenic or non-proteinogenic ones, modifications of peptide bond, and others. The studies revealed changes in the immunosuppressive potency of these analogs investigated in a number of in vitro and in vivo experimental models, predominantly in rodents, as well as differences in their postulated mechanism of action. The modified peptides were compared with cyclosporine A and parent CLA. Some of the synthesized and investigated peptides show potential therapeutic usefulness.

Cyclosporine A: Chemistry and Toxicity – A Review

: Cyclosporine A (CsA) is a cyclic undecapeptide with strong immunosuppressive potency. Firstly marketed in the mid-1980s, CsA was widely used in transplantation and greatly improved the survival rates of patients and grafts after solidorgan transplantation. Unfortunately, CsA administration can be associated with a number of side effects due to its high toxicity. These side effects seriously limited the clinical use of CsA. Therefore, it is important to understand the serious side effects of CsA in patients, especially in transplantation. In this review article, we are summarizing the chemistry and most known toxic effects of CsA including the nephrotoxic, hepatotoxic, neurotoxic and cardiotoxic effects. Its available toxicity data (different species, different administration routes) published formerly are also summarized. In addition, the molecular pathways of toxic damage induced by CsA are also detailly discussed. We hope that this review will help to further understand the source, chemistry and clinical application of CsA in patients as well as the potential mechanisms of CsA-induced toxicity.