Orosomucoid binding induced amplification of inherent chirality of the immunosuppressant drug sirolimus

Zsila, Ferenc (2015) Orosomucoid binding induced amplification of inherent chirality of the immunosuppressant drug sirolimus. RSC Advances, 5 (103). pp. 84523-84525. ISSN 2046-2069

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Abstract

Circular dichroism (CD) spectroscopic data indicate the conformational change of the triene moiety of the immunosuppressive agent sirolimus (rapamycin) upon its binding to human [small alpha]1-acid glycoprotein (orosomucoid). The development of an intense, negative [small pi] [rightward arrow] [small pi]* CD Cotton effect and the bathochromic shift of the corresponding UV band are attributed to the increased helical distortion of the conjugated [small pi]-system. Comparative chiroptical evaluation of the interaction of sirolimus with the separated genetic variants of orosomucoid suggests that the F1/S form is dominant in the amplification of inherent chirality of the triene chromophore while the A variant induces much weaker structural modification. Consistently, the drug binding affinities of the native protein and the F1/S variant estimated from the CD spectra are close to each other ([similar]2 [times] 105 M-1).

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