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

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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 α1-acid glycoprotein (orosomucoid). The development of an intense, negative π → π∗ CD Cotton effect and the bathochromic shift of the corresponding UV band are attributed to the increased helical distortion of the conjugated π-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 (∼2 × 105 M-1).

Original languageEnglish
Pages (from-to)84523-84525
Number of pages3
JournalRSC Advances
Volume5
Issue number103
DOIs
Publication statusPublished - Jan 1 2015

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ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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