Raman, SERS, and induced circular dichroism techniques as a probe of pharmaceuticals in their interactions with the human serum albumin and p-glycoprotein

Fabrice Fleury; Anatoli I. Ianoul; Loris Baggetto; Jean-Claude Jardillier; Alain J.P. Alix; Igor R. Nabiev

doi:10.1117/12.345387

9 April 1999 Raman, SERS, and induced circular dichroism techniques as a probe of pharmaceuticals in their interactions with the human serum albumin and p-glycoprotein

Fabrice Fleury, Anatoli I. Ianoul, Loris Baggetto, Jean-Claude Jardillier, Alain J.P. Alix, Igor R. Nabiev

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Proceedings Volume 3608, Biomedical Applications of Raman Spectroscopy; (1999) https://doi.org/10.1117/12.345387
Event: BiOS '99 International Biomedical Optics Symposium, 1999, San Jose, CA, United States

Abstract

Camptothecin (CPT) derivatives are the well known inhibitors of the human DNA topoisomerase (topo) I. Two of them, irinotecan and topotecan, are just in the clinics; 9-amino- CPT is on the stage II of clinical trials, and the active search for new derivatives is now in progress. Stability of the CPT derivatives on their way to the target and resistance of cancer cells to these drugs present the crucial problem of the chemotherapy. Human serum albumin (HSA) is the mediator of transport and metabolism of numerous pharmaceuticals in the blood and P-glycoprotein (P- gp) plays a crucial role of the mediator of the multidrug resistance (MDR) of the cancer cells. This paper present the result of analysis of molecular interactions of some drugs of CPT family with the HSA and P-gp. Induced circular dichroism (CD) and Raman techniques have been applied for monitoring molecular interaction of drugs with HSA as well as to identify the conformational transition of the protein induced by the drug binding. Drug molecular determinants responsible for interaction have been identified and their binding sites within the HSA have been localized. New cancer cells lines exhibiting an extremely high level of MDR resistance have been established and were shown to contain the P-gp overproduced in the quantities of 35 percent from the all membrane proteins. The membrane fractions of these cells with the controls presented by the membranes of the parental membrane proteins. The membrane fractions of these cells with the controls presented by the membranes of the parental sensitive cells may be used as a model system for spectroscopic analysis of the specific pharmaceuticals/P-gp interactions.

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Fabrice Fleury, Anatoli I. Ianoul, Loris Baggetto, Jean-Claude Jardillier, Alain J.P. Alix, and Igor R. Nabiev "Raman, SERS, and induced circular dichroism techniques as a probe of pharmaceuticals in their interactions with the human serum albumin and p-glycoprotein", Proc. SPIE 3608, Biomedical Applications of Raman Spectroscopy, (9 April 1999); https://doi.org/10.1117/12.345387

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KEYWORDS

Raman spectroscopy

Proteins

Cancer

Resistance

Spectroscopy

Molecular interactions

Systems modeling

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