Interactions of chlorpromazine with milk proteins.
The mode and nature of the binding of chlorpromazine (CPZ), a psychotropic drug, with milk proteins--alpha-lactalbumin (with substantial amounts of alpha-helix, beta-sheet and random coil), alpha-lactoglobulin (a major beta-sheeted protein) and alphas-casein (a random coiled protein) have been studied spectrofluorometrically and spectropolarimetrically. The binding affinity of CPZ for unfolded proteins is comparatively less than that of folded proteins although the number of binding sites is smaller in the latter case, due to the greater extent of binding of CPZ for folded proteins. Thermodynamic analysis reveals that CPZ binds to alpha-lactalbumin and alphas-casein in an endothermic (deltaH degrees is positive) and hydrophobic manner but with beta-lactoglobulin in an exothermic (deltaH degrees is negative) manner. Far UV Circular dichroic studies reveal that CPZ increases the secondary structure of the major beta-sheeted protein, beta-lactoglobulin possibly by increasing the relative contact orders (non-local contacts) within the residues. On the other hand, for proteins possessing random coil, it increases the unfolded state of the protein. CPZ does not affect local contacts in alpha-helix when its interaction is compared with a major alpha-helical protein, myoglobin.
Bhattacharyya
J
J
Department of Chemistry, Bose Institute, Calcutta, India. bhattacharyyaj@health.missouri.edu
Das
K P
KP
D014150:Antipsychotic Agents / Q000378:metabolism*; D001665:Binding Sites; D002364:Caseins / Q000737:chemistry / Q000378:metabolism; D002746:Chlorpromazine / Q000378:metabolism*; D002942:Circular Dichroism; D006801:Humans; D007768:Lactalbumin / Q000737:chemistry / Q000378:metabolism; D007782:Lactoglobulins / Q000737:chemistry / Q000378:metabolism; D008894:Milk Proteins / Q000737:chemistry* / Q000378:metabolism*; D009211:Myoglobin / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013053:Spectrophotometry; D013816:Thermodynamics
D014150:Antipsychotic Agents; D002364:Caseins; D007782:Lactoglobulins; D008894:Milk Proteins; D009211:Myoglobin; D007768:Lactalbumin; D002746:Chlorpromazine