Selectivity and stereospecificity of the reactions of dichlorodiammineplatinum(II) with three purified plasma proteins.
The reactions of cis- and trans-dichlorodiammineplatinum(II) (cis- and trans-DDP) with albumin and two plasma proteinase inhibitors were compared. Reaction with alpha 2-macroglobulin (alpha 2M) resulted in subunit crosslinking and loss of proteinase binding activity. The reaction also modified a receptor recognition site present on each alpha 2M subunit. While more trans-DDP was incorporated into alpha 2M than cis-DDP, cis-DDP was more effective at blocking receptor recognition, alpha 1-proteinase inhibitor was also inactivated by reaction with either cis- or trans-DDP. These reactions resulted in binding of platinum to methionine-358 at the reactive center of this inhibitor. Trans-DDP, however, was less selective and also bound to the single cysteine residue (Cys-232) of alpha 1PI. Reaction of albumin with cis-DDP resulted in incorporation of about 1 mol platinum per mol protein, and this platinum modified the single cysteine (Cys-34) in the molecule. Albumin incorporated twice as much trans-DDP, but the binding did not involve cysteine-34. In general, reactions of cis-DDP with proteins appear to be more selective than those observed for modification with the trans isomer.
Pizzo
S V
SV
Department of Pathology, Duke University, Durham, North Carolina.
Swaim
M W
MW
Roche
P A
PA
Gonias
S L
SL
D001798:Blood Proteins / Q000378:metabolism*; D002945:Cisplatin / Q000097:blood*; D006801:Humans; D007536:Isomerism; D007700:Kinetics; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000097:blood*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins / Q000378:metabolism*
D001798:Blood Proteins; D011480:Protease Inhibitors; D012709:Serum Albumin; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; C034697:transplatin; D002945:Cisplatin