Lipopolysaccharide Neutralizing Peptide–Porphyrin Conjugates for Effective Photoinactivation and Intracellular Imaging of Gram-Negative Bacteria Strains

Abstract

A simple and specific strategy based on the bioconjugation of a photosensitizer protophophyrin IX (PpIX) with a lipopolysaccharide (LPS) binding antimicrobial peptide YI13WF (YVLWKRKRKFCFI-Amide) has been developed for the effective fluorescent imaging and photodynamic inactivation of Gram-negative bacterial strains. The intracellular fluorescent imaging and photodynamic antimicrobial chemotherapy (PACT) studies supported our hypothesis that the PpIX-YI13WF conjugates could serve as efficient probes to image the bacterial strains and meanwhile indicated the potent activities against Gram-negative bacterial pathogens especially for those with antibiotics resistance when exposed to the white light irradiation. Compared to the monomeric PpIX-YI13WF conjugate, the dimeric conjugate indicated the stronger fluorescent imaging signals and higher photoinactivation toward the Gram-negative bacterial pathogens throughout the whole concentration range. In addition, the photodynamic bacterial inactivation also demonstrated more potent activity than the minimum inhibitory concentration (MIC) values of dimeric PpIX-YI13WF conjugate itself observed for E. coli DH5a (∼4 times), S. enterica (∼8 times), and other Gram-negative strains including antibiotic-resistant E. coli BL21 (∼8 times) and K. pneumoniae (∼16 times). Moreover, both fluorescent imaging and photoinactivation measurements also demonstrated that the dimeric PpIX-YI13WF conjugate could selectively recognize bacterial strains over mammalian cells and generate less photo damage to mammalian cells. We believed that the enhanced fluorescence and bacterial inactivation were probably attributed to the higher binding affinity between dimeric photosensitizer peptide conjugate and LPS components on the surface of bacterial strains, which were the results of efficient multivalent interactions.

Charged Triazole Cross-Linkers for Hyaluronan-Based Hybrid Hydrogels

“…Subsequent hydrazinolysis [35] proceeded uneventfully, and the resulting diaminotriazoles 12 were converted to the bismaleimidotriazoles 2 by treatment with maleic anhydride and NEt 3 , followed by reaction with Ac 2 O and NaOAc according to the procedure by Liu [36] with a 17%–29% yield over three steps. The yield for the maleimide cross-linkers was quite low due to the formation of several by-products during the last two steps, such as the addition of AcOH to the maleimides.…”

Antibacterial photodynamic therapy: overview of a promising approach to fight antibiotic-resistant bacterial infections

“…In terms of APDT efficacy, an LPS-neutralizing peptide YI13WF (YVLWKRKRKFCFI-amide) conjugated to protophophyrin IX was shown to have high killing potential in E. coli and Klebsiella pneumoniae [199]. Since protoporphyrin is taken up by mammalian cells as well, some photosensitization of non-target cells is expected.…”

Synthesis and Study of New N-Substituted Hydrazones of Ni(II) Complexes of β-Octaethylporphyrin and Coproporphyrin I Tetraethyl Ester

“…Due to their unique photophysical and photochemical properties, porphyrins and metalloporphyrins are used as various sensors in bioanalysis, [1,2] active substances of drugs in the diagnosis and therapy of cancer. [3] The fundamental task, addressed by numerous studies in the fields of bioorganic and medical chemistry, is the creation of new drugs based on porphyrin conjugates with various biologically active compounds and other functional fragments, [4][5][6][7] having specified properties, such as low toxicity, hydrophilicity, high selectivity of accumulation and distribution in affected cells and tissues. Palladium-catalyzed cross-coupling reactions are widely used to produce various functionalized derivatives of mono-and oligoporphyrins, which possess practically useful properties.…”