4-Methylpseudoproline analogues of cyclolinopeptide A: Synthesis, structural analysis and evaluation of their suppressive effects in selected immunological assays (original) (raw)
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Molecules
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.
Journal of Peptide Science, 2009
9 -), isolated from linseed oil, was found to possess a strong immunosuppressive activity comparable, in low doses, with that of CsA, with a mechanism that depends on the inhibition of the interleukin-1 and interleukin-2 action. Structural analysis of CLA and its related compounds has underlined that the presence of the tetrapeptide Pro-Pro-Phe-Phe sequence, the Pro-Pro cis amide bond, and the 'edge-to-face' interaction are possible important features for the immunosuppressive activity of CLA. To evaluate the role and significance of 'edge-to-face' interaction in the process of molecular recognition by receptors, we have synthesised three linear precursors and three cyclic analogues of CLA, in which one or both Phe residues have been replaced by β 3 Phe residues. A conformational analysis by NMR in CD 3 CN/H 2 O mixture has been carried out on the CLA analogue, in which Phe 3 has been replaced by a βPhe, to study the influence of the mutation on the three-dimensional structure. All linear and cyclic CLA analogues containing βPhe have been tested in the humoral and cellular immune response in vivo assays in mice. The peptide activities have been compared with CsA, as a reference drug.
Sulfonated analogues of cyclolinopeptide A Synthesis, immunosuppressive activity and CD studies
The Journal of Peptide Research, 2009
Linear and cyclic analogues of cyclolinopeptide A (CLA) in which one or both phenylalanine residues in fragment Pro6-Pro7-Phe8-Phe9 were substituted by their sulfonated derivatives have been synthesized by SPPS method and cyclization with the BOP reagent. The peptides were examined for their immunosuppressive activity in the humoral and cellular immune response by PFC and DTH tests. All of the analogues retain some immunosuppressive activity of native CLA. Their CD spectra confirm that the optical activity of aromatic residues in CLA depends on their position in the peptide chain. Only the residue in position 8 seems to be optically active. CD spectrum of the cyclic analogue modified in position 9 is very similar to that of native CLA which correlates with its high biological activity. The chiroptical properties of the p-sulfonated Phe-residue are established.
Analogues of cyclolinopeptide a containing α‐hydroxymethyl amino acid residues
Peptide …, 2005
The present article is dedicated to our mentor and friend Murray Goodman, who devoted his scientific activity to encourage laboratories and scientists from all over the world to explore the potentialities of peptides. The research group of Naples became part of the peptide community thanks to the stimulus and help constantly given by Murray.
Analogues of cyclolinopeptide a containing ?-hydroxymethyl amino acid residues
Biopolymers, 2005
The present article is dedicated to our mentor and friend Murray Goodman, who devoted his scientific activity to encourage laboratories and scientists from all over the world to explore the potentialities of peptides. The research group of Naples became part of the peptide community thanks to the stimulus and help constantly given by Murray.
Ala analogues of the cyclolinopeptide A
Biopolymers, 1989
Sapienza," R o m ; TEODORICO TANCREDI, ICMIB del CNR, Arco Felice, Napoli; FILOMENA ROSSI, E?TORE BENEDE'ITI, CARL0 PEDONE,* and PIERANDREA TEMUSSI, Diparthento di Chimica, Via Mezzocannone, 4 (80134) Napoli, I t a h Synopsis Analogues of cyclolinopeptide A, due to the replacement of each amino acid in the Prd-fig-Phe3-Phe4 sequences with an LAla residue, were synthesized by classical method in solution. Mixed anhydride and N,N-dicyclohexylcarbodiimide coupling methods have been used for the synthesis of both linear and cyclic peptides. The produds were characterized by Rf values and uv spectra, as well as by fast atom bombardment spectroscopy.
Anticancer Potential of the Cyclolinopeptides
Cancers
Novel therapeutic agents to combat cancer is an active area of research, as current treatment options have limitations in efficacy and tolerability. One of these therapeutic agents in our immediate environment is cyclolinopeptides (CLPs). CLPs have several advantages that make them suitable for daily consumption and potential therapeutics in cancer research. They are natural compounds, having high specificity, low toxicity, low cost, and an overall simple extraction process. Over the years, numerous in vitro studies in cancer cells demonstrated CLPs to possess anti-proliferative, apoptotic, and anti-angiogenic effects, as well as the ability to induce cell cycle arrest and inhibit cancer cell growth in various cancer types, including breast cancer, gastric cancer, and melanoma. This paper provides an overview of the significance and potential of CLPs as therapeutic agents, emphasizing their promising role in cancer treatment based on different cancer cell lines. The mechanism of act...
Archivum immunologiae et therapiae experimentalis, 1999
The results of the investigation of immunosuppressive activity of cyclolinopeptide A (CLA--cyclic hydrophobic nonapeptide present in the linseeds) and its analogs are discussed. The results obtained for other natural cyclic peptides showing structural similarities with CLA (antamanide, cycloamanides, hymenistatin, hymenamides) are also reviewed. It results from these investigations that the molecular mechanism of the CLA action is the same as that of cyclosporin A and FK-506 compound, i.e. it consists in formation of the complex with cyclophilin and inhibition--in this form--of the phosphatase activity of calcineurin. The results also suggest that the immunosuppressive activity of these compounds resides in their--Pro-Xxx-Phe- fragment, where Xxx is a hydrophobic (e.g. Leu, Val) or aromatic amino acid residue.