Siderophilin metal coordination. 1. Complexation of thorium by transferrin: structure-function implications

Journal Article · Wed May 06 04:00:00 EDT 1981 · J. Am. Chem. Soc.; (United States)

DOI:https://doi.org/10.1021/ja00399a016· OSTI ID:6205121

Harris, W R; Carrano, C J; Pecoraro, V L; Raymond, K N

As part of a program to develop actinide-specific sequestering agents, the coordination of actinide ions by human transferrin is being investigated. Therapeutically useful synthetic ligands must be able to compete with this iron-transport protein for the bound actinide ion. As in the Fe(III) complex of the native protein, two Th(IV) ions bind at pH 7. This coordination has been monitored at several pH values by using difference ultraviolet spectroscopy. The corresponding coordination of a phenolic ligand, ethylenebis(o-hydroxyphenylglycine) (EHPG), has been used to determine ..delta..epsilon upon protein coordination, the number of transferrin tyrosine residues that coordinate. Maxima in the Th(IV) + EHPG difference UV spectra occur at 292 and 238 nm, with corresponding ..delta..epsilon values per phenolic group of 2330 and 8680 cm/sup -1/ M/sup -1/, respectively. At pH 7.2, the Th(IV) transferring spectrum is closely similar to the Th/sup IV/EHPG spectrum, with maxima at 292 and 240 nm. The ..delta..epsilon at 240 nm reaches a maximum of 24700 cm/sup -1/ m/sup -1/, which corresponds to coordination of three tyrosine residues in the dithorium-transferrin complex; the stronger binding site (A or C-terminal) coordinates via two tyrosines and the weaker (B or N-terminal) via one. There is evidence suggesting that the N-terminal site is slightly smaller than the C-terminal site; while Th(IV) easily fit into both sites.s into the C-terminal site, the large ionic radius of Th(IV) makes this ion of borderline size to fit into the N-terminal site. This may be an important biological difference between Th(IV) and the slightly smaller Pu(IV), which should easily fit into both sites.

• Research Organization: Lawrence Berkeley Lab., CA
• OSTI ID: 6205121
• Journal Information: J. Am. Chem. Soc.; (United States), Journal Name: J. Am. Chem. Soc.; (United States) Vol. 103:9; ISSN JACSA
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400702* -- Radiochemistry & Nuclear Chemistry-- Properties of Radioactive Materials
ACTINIDE COMPLEXES
ACTINIDES
AMINO ACIDS
AROMATICS
CARBOXYLIC ACIDS
COMPLEXES
COMPLEXOMETRY
DATA
ELEMENTS
EXPERIMENTAL DATA
FUNCTIONS
GLOBULINS
GLOBULINS-BETA
HYDROXY ACIDS
HYDROXY COMPOUNDS
INFORMATION
LIGANDS
METALLOPROTEINS
METALS
NUMERICAL DATA
ORGANIC ACIDS
ORGANIC COMPOUNDS
PH VALUE
PHENOLS
PROTEINS
SPECTRA
STRUCTURE FUNCTIONS
THORIUM
THORIUM COMPLEXES
TRANSFERRIN
TYROSINE
ULTRAVIOLET SPECTRA