Tumor-specific protein human galectin-1 interacts with anticancer agents.
The present work shows a novel binding activity of the tumor specific lectin--recombinant human galectin-1 (hGal-1)--to three porphyrin compounds: (1) Zn-porphyrin (ZnTPPS); (2) Mn-porphyrin and (3) Au-porphyrin. These compounds are widely applied in the photodynamic therapy of cancer (PDT). Our data indicate that hGal-1, similar to some plant lectins, a bacterial lectin from Pseudomonas aeruginosa and an animal lectin from Helix pomatia, possesses dual functions binding to both carbohydrate and non-carbohydrate ligands. The interaction of ZnTPPS with hGal-1 was studied by the specific fluorescence emission of the porphyrin. The protein binding properties to Mn/Au-porphyrins and adenine were measured by intrinsic protein fluorescence quenching. The values determined for the apparent dissociation constants (K(D)) of 0.6-1.5 microM are similar to the K(D) for complexes of concanavalin A and porphyrin, and are indicative of the high affinity of hGal-1 for these porphyrins. In addition, the analysis of the hyperbolic binding curves obtained suggests the presence of one hGal-1 binding site for porphyrins or adenine. Additionally, we found that hGal-1 interacts with the fluorescent probe 2-(p-toluidinyl)naphthalene sulfonic acid (TNS), that was used to identify the hydrophobic regions within hGal-1. Homodimeric hGal-1 has more than one class of binding site for TNS as revealed by the sigmoidal shape of the fluorescence titration curve. hGal-1 can be characterized as a porphyrin-binding protein based on its interactions with the Zn/Mn- and Au-porphyrins, and this indicates that hGal-1 may have potential as a delivery molecule to target systems (e.g., tumor cells) with possible application in photodynamic therapy.
D'Auria
Sabato
S
Laboratory for Molecular Sensing, Institute of Protein Biochemistry, CNR, Via P. Castellino, 111, 80131 Naples, Italy.
Petrova
Lidia
L
John
Constance
C
Russev
George
G
Varriale
Antonio
A
Bogoeva
Vanya
V
D016588:Anticarcinogenic Agents / Q000737:chemistry* / Q000378:metabolism*; D037483:Galectin 1 / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010778:Photochemotherapy / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry* / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D037483:Galectin 1; D008665:Metalloporphyrins; D011994:Recombinant Proteins