PT - JOURNAL ARTICLE AU - COLIN F. CHIGNELL AU - DONNAS K. STARKWEATHER TI - Optical Studies of Drug-Protein Complexes DP - 1971 May 01 TA - Molecular Pharmacology PG - 229--237 VI - 7 IP - 3 4099 - http://molpharm.aspetjournals.org/content/7/3/229.short 4100 - http://molpharm.aspetjournals.org/content/7/3/229.full SO - Mol Pharmacol1971 May 01; 7 AB - When acetylsalicylic acid is incubated at 37° with human serum albumin the protein is acetylated by the drug. Acetylation of human serum albumin by acetylsalicylic acid does not appear to cause any conformational changes, since the intrinsic optical activity of the protein is unaltered. However, the positive extrinsic Cotton effect generated at 287 mµ by the binding of phenylbutazone to human serum albumin increased in amplitude after the protein had been acetylated by acetylsalicylic acid. In contrast, the strong positive extrinsic circular dichroic band which appears at 296 mµ when flufenamic acid binds to human serum albumin decreased in amplitude when the protein was acetylated by acetylsalicylic acid, while the weaker negative band at 345 mµ was unchanged. Acetylsalicylic acid treatment of human serum albumin did not affect the strong negative extrinsic circular dichroic band at 305 mµ generated by the binding of dicoumarol. These results suggest that acetylation of human serum albumin by acetylsalicylic acid specifically modifies the binding sites for phenylbutazone and flufenamic acid. No change in the extrinsic optical activity of bound phenylbutazone or flufenamic acid was observed when acetylsalicylic acid was replaced by salicylic acid or by other acylating agents such as benzylpenicillin, benzylpenicillenic acid, and acetic anhydride. Equilibrium dialysis measurements showed that acetylation by acetylsalicylic acid also increased the affinity of human serum albumin for phenylbutazone but decreased its affinity for flufenamic acid. The affinity of the acetylsalicylic acid-treated human serum albumin for dicoumarol was the same as that of albumin incubated alone. Thus the plasma binding of phenylbutazone or flufenamic acid in a patient may be altered by the prior ingestion of acetylsalicylic acid.