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The Role of the Peripheral Benzodiazepine Receptor in Photodynamic Activity of Certain Pyropheophorbide Ether Photosensitizers: Albumin Site II as a Surrogate Marker for Activity ¶
Author(s) -
Dougherty Thomas J.,
Sumlin Adam B.,
Greco William R.,
Weishaupt Kenneth R.,
Vaughan Lurine A.,
Pandey Ravindra K.
Publication year - 2002
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2002)0760091trotpb2.0.co2
Subject(s) - chemistry , in vivo , photodynamic therapy , photosensitizer , binding site , in vitro , human serum albumin , ether , ligand (biochemistry) , benzodiazepine , biological activity , stereochemistry , albumin , chlorin , active site , receptor , biochemistry , enzyme , photochemistry , organic chemistry , biology , microbiology and biotechnology
A study has been carried out to define the importance of the peripheral benzodiazepine receptor (PBR) as a binding site for a series of chlorin‐type photosensitizers, pyropheophorbide‐a ethers, the subject of a previous quantitative structure–activity relationship study by us. The effects of the PBR ligand PK11195 on the photodynamic activity have been determined in vivo for certain members of this series of alkyl‐substituted ethers: two of the most active derivatives (hexyl and heptyl), the least active derivative (dodecyl [C12]) and one of intermediate activity (octyl [C8]). The photodynamic therapy (PDT) effect was inhibited by PK11195 for both of the most active derivatives, but no effect on PDT activity was found for the less active C12 or C8 ethers. The inhibitory effects of PK11195 were predicted by the binding of only the active derivatives to the benzodiazepine site on albumin, i.e. human serum albumin (HSA)‐Site II. Thus, as with certain other types of photosensitizers, it has been demonstrated with this series of pyropheophorbide ethers that in vitro binding to HSA‐Site II is a predictor of both optimal in vivo activity and binding to the PBR in vivo.