Near-infrared porphyrin photosensitisers combined with a cationic peptide for targeted antimicrobial PDT

The emergence of bacteria and fungi which display multidrug-resistance towards antibiotics constitutes a major health problem, responsible for millions of deaths every year all over the world.[1] An alternative to antibiotics consists in the use of the aPDT (antimicrobial PhotoDynamic Therapy) to destroy drug resistant bacteria without inducing new resistances.[2] This treatment consists of the light activation of a photosensitiser (PS) of suitable wavelength to produce reactive oxygen species that destroy bacteria. For a selective and efficient aPDT treatment, one approach is to conjugate the PS with an AMP (AntiMicrobial Peptide). Such association has shown encouraging results on gram-positive and gram-negative bacteria.[3] Our goal is to develop new photoactivable antibacterial drugs, which combine PS activated in the optical therapeutic window with AMPs to increase the selectivity of the treatment. Antibacterial agents composed of porphyrins linked to a PGLa peptide have been synthesised (Figure 1). The design of the PS, extended ?-conjugated system over a ?-acceptor, enables its activation in the near-infrared to prevent photodamage to healthy tissue. It was associated to a cationic peptide, PGLa, a peptide known for its selective interaction with bacterial membranes.[4] The synthesis of the PS-AMP conjugates as well as the studies on E. Coli bacteria will be presented.