title: The effects of substituted cyclodextrins on the colloidal and conformational stability of selected proteins.
abstract: The effects of various types of substituted and nonsubstituted cyclodextrins (CDs) on the physical and colloidal stability of three different proteins were studied to further ascertain the mechanism by which cyclodextrins stabilize proteins. The three proteins examined in this study are the Clostridium difficile Toxoid A, Yersinia pestis low-calcium-response V or V antigen (LcrV), and fibroblast growth factor 10 (FGF-10). These three pharmaceutically relevant proteins differ in molecular weight, pI, as well as in their secondary and tertiary structure. The effects of three parent cyclodextrins (alpha, beta, and gamma), as well as several hydroxypropyl (HP-CDs) and sulfobutylether (SBE-CDs) cyclodextrins of varying degrees of substitution, on the three proteins were examined as a function of pH and temperature. Structural changes and aggregation behavior were monitored in the presence and absence of the 17 cyclodextrins using circular dichroism, intrinsic fluorescence spectroscopy, and static light scattering. Overall, the major effect of the cyclodextrins on the proteins was the ability of a majority of them to inhibit thermally induced aggregation. This study suggests that the stabilization of proteins by cyclodextrins is dictated by their type and degree of substitution, as well as the physical and chemical properties of the protein being examined.
authors.affiliation: Department of Pharmaceutical Chemistry, Macromolecule and Vaccine Stabilization Laboratory, University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Hardeep S
authors.initials: HS
authors.lastname: Samra
authors.forename: Feng
authors.initials: F
authors.lastname: He
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Bhambhani
authors.forename: J D
authors.initials: JD
authors.lastname: Pipkin
authors.forename: Roz
authors.initials: R
authors.lastname: Zimmerer
authors.forename: Sangeeta B
authors.initials: SB
authors.lastname: Joshi
authors.forename: C Russell
authors.initials: CR
authors.lastname: Middaugh
mesh_terms: D002942:Circular Dichroism; D016360:Clostridioides difficile / Q000737:chemistry*; D003505:Cyclodextrins / Q000737:chemistry*; D008968:Molecular Conformation; D008970:Molecular Weight; D011506:Proteins; D013050:Spectrometry, Fluorescence; D013696:Temperature
chemical_list: D003505:Cyclodextrins; D011506:Proteins