Synthetic approaches for the conjugation of porphyrins and related macrocycles to peptides and proteins

Abstract

The association of photosensitisers to peptides and proteins is a recognised and successful method for enhancing the selectivity and efficacy of photodynamic treatment. The covalent attachment of porphyrins and related macrocycles to peptides and proteins can generate new phototoxic species that allow the concentration of the oxidative damage to the target area, thanks to their enhanced cellular uptake, favourable sub-cellular distribution, and ability to target receptors or enzymes over-expressed by a given tissue or cell. The need to exert control over the regioselectivity of the conjugation led to the exploration of a variety of chemistries; in some cases based on bioorthogonal ligations, in others exploring the reactivity of naturally occurring functional groups. In this review we place a major emphasis on the synthetic strategies adopted to generate such conjugates. All such strategies will be surveyed, together with the methods used to introduce or unmask the appropriate reactive functionalities both on the peptide moiety and the photosensitiser.

Porphyrin-based cationic amphiphilic photosensitisers as potential anticancer, antimicrobial and immunosuppressive agents

“…This so-called active targeting is accomplished by conjugating PSs to monoclonal antibodies, tumour-homing and cell-penetrating peptides. Such conjugates can be prepared through synthesis of porphyrins and the related compounds bearing amine-reactive functional groups to ensure stable covalent bonding with biomolecules, and cationic moieties within porphyrins structure can facilitate conjugation by improving their water solubility (Giuntini et al 2011). Several water-soluble cationic diphenyland tetraphenyl-porphyrins with an isothiocyanate group were synthesised and successfully conjugated to a range of monoclonal antibodies (anti-EpCAM, anti-CD146, anti-CD104, anti-CD326).…”

mTHPC – A drug on its way from second to third generation photosensitizer?

“…Peptide and protein bioconjugates of porphyrins present the most logical route towards this end. Significant advances have been made with various peptide appended porphyrin systems and Boyle and coworkers have covered this field in a recent review [93]. Glycoporphyrins complement this approach and open new possibilities through lectin targeting.…”

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…In recent years this research has expanded to incorporate bioactive functionalities for targeting. One such example was the introduction of amino acids/peptide conjugates to either increase cellular uptake of the porphyrin derivative or delivery of the peptidic units to nucleic acids [44,[371][372][373][374] . One such recent example includes cationic porphyrins with Mn complexation which have been covalently linked with peptide cell signaling sequences.…”

“…These include porphyrins with steroids, lipids, peptides, carbohydrates, lectins and nucleotides. Especially for porphyrins with signaling peptides a significant body of information is now available [44][45][46][47][48] . Porphyrins appended with amino acids have been prepared to model haemoproteins [49][50][51] , to investigate ligand binding and oxygenative catalysis and energy transfer in photosynthesis [52] .…”