Binding of porphyrin to human serum albumin. Structure–activity relationships

Cohen, Smadar; Margalit, Rimona

doi:10.1042/bj2700325

Cited by 67 publications

(41 citation statements)

References 38 publications

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“…This finding is in accordance with earlier studies with a similar porphycene (Guardiano et al, 1989). The porphyrins in photofrin will probably form aggregates in watery solutions or, upon injection, become associated with serum proteins (Cohen & Margalit, 1990). The negligible uptake of ATPPn Figure 5.…”

Section: Discussionsupporting

confidence: 81%

“…The permeability hypothesis might also explain the selectivity found for a wide range of different photosensitisers (Gomer, 1991), many of which were shown to have an affinity to macromolecular carrier particles in the bloodstream, like lipoproteins or albumin (Cohen et al, 1990). In accordance with this 'vascular' localisation process, no difference in sensitiser uptake had been found between malignant and non-malignant cell lines in vitro (Moan et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster

Leunig

Richert²,

Gamarra³

et al. 1993

Br J Cancer

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Summary In this study the localisation of porphyrinoid photosensitisers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitisers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitisers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 ± 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitisers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers.In the first half of this century it was shown that systemically administered porphyrines preferentially localise in neoplasms of tumour-bearing animals (Policard, 1924;Auler et al., 1942). This phenomenon found diagnostic application as a method for tumour detection utilising the red fluorescence of the porphyrines (Lipson et al., 1961a,b;Baumgartner et al., 1987). The photosensitising properties of these molecules (Meyer-Betz, 1913) were exploited for therapeutic purposes and allowed the establishment of photodynamic therapy (PDT) as a new treatment modality for tumours (Dougherty et al., 1978).The mechanisms leading to the tumour specific localisation of the porphyrines are still under investigation (Moan et al., 1992). Experimental progress has been complicated by the fact that even the most purified photosensitiser, Photofrin (Pf), is a complex mixture of molecular species with very similar spectral characteristics (Dougherty, 1987;Pandey et al., 1990).In the present investigation, the localisation of three chemically pure synthetic porphyrinoids in an amelanotic mel...

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster

Leunig

Richert²,

Gamarra³

et al. 1993

Br J Cancer

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“…In total, our results suggest that the HmuR binding site for heme has an axial histidine and accommodates a porphyrin structure with a periphery approximating that of the natural substrate hemin at the 2 and 4 positions. It should also be noted that differentialreconstitution experiments are subject to the issues that the porphyrins and metalloporphyrins may bind to other components in the mixture (20), that proteins and lipids interacting with one another may change the constant for binding to any individual component (8,32), and that porphyrins and metalloporphyrins can aggregate in aqueous solution (7,9,27).…”

Section: Discussionmentioning

confidence: 99%

Binding Specificity of the Porphyromonas gingivalis Heme and Hemoglobin Receptor HmuR, Gingipain K, and Gingipain R1 for Heme, Porphyrins, and Metalloporphyrins

2001

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Previous genetic and biochemical studies have confirmed that hemoglobin and hemin utilization in Porphyromonas gingivalis is mediated by the outer membrane hemoglobin and heme receptor HmuR, as well as gingipain K (Kgp), a lysine-specific cysteine protease, and gingipain R1 (HRgpA), one of two arginine-specific cysteine proteases. In this study we report on the binding specificity of the recombinant P. gingivalis HmuR protein and native gingipains for hemoglobin, hemin, various porphyrins, and metalloporphyrins as assessed by spectrophotometric assays, by affinity chromatography, and by enzyme-linked immunosorbent assay. Protoporphyrin, mesoporphyrin, deuteroporphyrin, hematoporphyrin, and some of their iron, copper, and zinc derivatives were examined to evaluate the

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“…possible with reduced costs of lasers and with the development of new laser types (argon ion laser, gold vapor laser). Moreover, in the fu ture it will be possible to achieve deeper tissue penetration and more exact targeting with the contact laser technique [57], The accumula tion of photosensitizing compounds in the tumor can still be further improved by com bining them with human serum albumin, with tumor-specific monoclonal antibodies or lipo proteins (LDL) or by applying them directly to the tumor [ 12,21,[58][59][60][61]. Other possibili ties would be the discovery of new photosen sitizing agents with optimal specificity in tu mor accumulation, absorbance in the far visi ble red or near infrared range and no toxicity for normal tissues or the use of multiple pho tosensitizers and wavelengths in PDT [62], Such improvements would broaden the clini cal applications of PDT to gastroenterology and gastrointestinal tumors and permit treat ment of more advanced malignancies.…”

Section: Miscellaneous Gastrointestinal Tumorsmentioning

confidence: 99%

Photodynamic Therapy of Gastrointestinal Tumors: A Review

Puolakkainen

Schröder

1992

Dig Dis

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Photodynamic therapy (PDT) is a new modality of cancer treatment. It consists of intravenously injecting a patient with a photosensitizing agent and, when this agent has accumulated in tumor cells, decomposing it by exposure to red light produced by an argon dye laser. Toxic compounds produced in this reaction then destroy the malignant cells, while normal tissue is not significantly affected. Most clinical experience with PDT has been gained in the treatment of lung cancer, cancer of the urinary bladder and malignancies of the head and neck region. In gastroenterology, esophageal, gastric and colonic tumors have clinically been treated with PDT. This paper is to review the current use of PDT in the treatment of gastrointestinal tumors.

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Binding of porphyrin to human serum albumin. Structure–activity relationships

Abstract: The equilibrium binding of hydroxyethyl vinyl deuteroporphyrin (HVD)

Cited by 67 publications

References 38 publications

Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster

Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster

Binding Specificity of the Porphyromonas gingivalis Heme and Hemoglobin Receptor HmuR, Gingipain K, and Gingipain R1 for Heme, Porphyrins, and Metalloporphyrins

Photodynamic Therapy of Gastrointestinal Tumors: A Review

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