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Synthesis, redox properties and conformational studies of multiple cystine/ selenocystine containing peptides

Objective



Research objectives and content
The diselenide bridge will be analyzed as mimetic of the disulfide bridge in term of oxidative folding behaviour and conformation of poly-cystine containing peptides. Endothelin- 1 and Apamin, with two intrachain disulfide bridge, are choosen as model peptides. With the rational substitution of one pair of cysteines with one pair of selenocysteines each time, formation of all possible monomeric conformers (globule, ribbon and beads) of these peptides will be induced and the conformations of the resulting fully and partially oxidized peptides will be investigated in order to define the conformational aspects of oxidative refolding pathways.
Conformational constraints will be applied to fragments peptide of the active site of four thiol protein oxidoreductases (PDI, grx, grr, trr), in the attempt to modulate in a favorable manner their redox potential for their use as PDI-like synthetic enzimes or folding adjuvants for recombinant proteins.
Training content (objective, benefit and expected impact)
My primary objective during this training is to acquire a deeper knowledge on the chemistry and biochemistry of cystine containing peptides that is still one of the more challenging fields in peptide chemistry. The contribution of Prof. Moroder in this field is worldwide known. I will also deal with other important biophysical aspects in peptide and protein chemistry, such as protein folding pathways and related conformational studies, to complete my training.
Links with industry / industrial relevance (22)
The correct oxidative folding of recombinant proteins still represent one of the major drawbacks for the industrial production of proteins as drugs. The development of low mass redox-active peptides with tunable redox potentials as folding adjuvants could be of decisive industrial relevance. In this context a link is established with NIGU Chemie Gmbh, Waldkreiburg, Germany

Funding Scheme

RGI - Research grants (individual fellowships)

Coordinator

MAX-PLANCK-GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN E.V.
Address
18A,am Klopferspitz 18 A
82152 Martinsried
Germany

Participants (1)

Not available
Italy