Biophysical characterisation of cationic peptides

Lahiri, Aritraa (2015) Biophysical characterisation of cationic peptides. Masters thesis, Indian Institute of Science Education and Research Kolkata.

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Abstract

Cationic cell penetrating peptides are harnessed as molecular transporters for delivering therapeutic biomolecules. We have designed amphipathic and oligoarginine based cationic peptides as molecular transporters and the preliminary uptake studies of these designed peptides suggest that depending on the nature of sequences, endocytic or combination of both endocytic and direct translocation across the cell membrane are the possible mechanism of cellular uptake. Recent theories propose that the binding of cationic cell penetrating peptides to negatively charged extracellular glycosaminoglycans (GAGs) such as heparan sulfate (HS) and heparin via endocytosis is a possible mechanism of cellular uptake. We have systematically studied three facial and two oligoarginine peptides with heparin to examine their conformational changes and clustering ability in presence of heparin. The circular dichroism studies revealed that heparin induces conformational changes both in oligoarginine and facial cationic peptides. Dynamic light scattering data suggests that both cationic and hydrophobic effect induces heparin clustering, but the hydrophobic interactions appear to be superior to electrostatic interactions in the aggregation process. We have also studied the cationic peptides’ interactions with DNA to elucidate the conformational changes of DNA in the presence of cationic peptides as well as the DNA loading efficiency of the molecular transporters.

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