Chemical derivatization and cellular imaging of immunosuppressive peptides

Mina Krasimirova Vasileva
2014 unpublished
Cyclotides have been isolated from plants of the families of Rubiaceae, Violaceae and Cucurbiceae and contain 28 to 37 amino acid residues which correspond to a mass range of 2500 – 4000 Da. They are circular proteins that are characterized by a head to tail cyclized backbone. At the molecular core of the peptides are three disulfide bonds which form a cyclic cystine knot. This structural motif is responsible for the stability and for the resistance of the cyclotides to thermal, chemical and
more » ... ymatic degradation. Moreover, these cyclic peptides are hydrophobic and this leads to a typical late elution from a RP–HPLC column. The history of cyclotides may be traced back at more than 50 years ago when Sandberg reported that African tribes have been using an extract from the plant Oldenlandia affinis to facilitate childbirth. Later the Norwegian doctor Lorents Gran made ethno botanical investigations and determined that it contained cyclic peptides which are responsible for the strong activity. Due to the previously investigated uterotonic activity, cyclotides got interested for scientists. Further research determined many other biological actions, including antimicrobial, insecticidal, anticancer, anti-HIV and immunosuppressive activity. To perform all these biological properties, the cyclotide interacts firstly with the cellular membrane of the living organisms. Moreover, the different subfamilies of cyclotides possess diverse mode of action. However, for all of them there is electrostatic interaction between the peptide and the cellular membrane due to the positively charged residues of the cyclotide and the negatively charged membrane head groups. Recent research reported that a mutant from the cyclotide kalata B1, where the threonine at position twenty is exchanged with a lysine, has an antiproliferative effect on lymphocytes. Although the main mechanism of action is still unclear, the cyclotide [T20K] kalata B1 suppresses the proliferation of T-cells. Moreover, the aim of this study was to confirm, impleme [...]
doi:10.25365/thesis.34235 fatcat:yq74ndlb5jc3dobyugwv6lvoz4