Extending the hydrophobic cavity of beta-cyclodextrin results in more negative heat capacity changes but reduced binding affinities

Jens Christian Sidney Schönbeck, Rene Holm, Peter Westh, Günther H. Peters

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    The formation of inclusion complexes of hydroxypropylated β-cyclodextrins (CDs) with three bile salts are investigated to shed light on the role played by the hydroxypropyl (HP) substituents. The HP-chains are situated at the rim of the CD and may thus extend the hydrophobic cavity of the CD. Calorimetric titrations in a broad temperature range and molecular dynamics simulations confirm previous speculations that the HP-chains cause an increase in dehydrated nonpolar surface area upon formation of the complexes. This additional burial of nonpolar surface area, 12–16 Å2 per HP-chain according to the MD simulations, results in more negative values of ΔC p °, which are in quantitative agreement with what is expected for hydrophobic dehydration. Although these observations support the picture of an extended hydrophobic cavity, HPβCD complexes were less stable than their unsubstituted counterparts. This indicates that increased hydrophobic contacts are not always accompanied by increased binding strength. The linear dependence of ΔC p °, ΔH° and ΔS° on the number of HP-chains give rise to isoentropic and isoenthalpic temperatures at which ΔH° and ΔS° are independent of the number of HP-chains on the host CD (but depend on the type of bile salt). Interestingly, these convergence temperatures are close to what is observed for unfolding of proteins and may be a common feature of hydrophobic dehydration
    OriginalsprogEngelsk
    TidsskriftJournal of Inclusion Phenomena and Macrocyclic Chemistry
    Vol/bind78
    Udgave nummer1-4
    Sider (fra-til)351-361
    ISSN1388-3127
    DOI
    StatusUdgivet - 2014

    Citer dette

    @article{678ba8d3e1b24f798837ec28ce72c7dc,
    title = "Extending the hydrophobic cavity of beta-cyclodextrin results in more negative heat capacity changes but reduced binding affinities",
    abstract = "The formation of inclusion complexes of hydroxypropylated β-cyclodextrins (CDs) with three bile salts are investigated to shed light on the role played by the hydroxypropyl (HP) substituents. The HP-chains are situated at the rim of the CD and may thus extend the hydrophobic cavity of the CD. Calorimetric titrations in a broad temperature range and molecular dynamics simulations confirm previous speculations that the HP-chains cause an increase in dehydrated nonpolar surface area upon formation of the complexes. This additional burial of nonpolar surface area, 12–16 {\AA}2 per HP-chain according to the MD simulations, results in more negative values of ΔC p °, which are in quantitative agreement with what is expected for hydrophobic dehydration. Although these observations support the picture of an extended hydrophobic cavity, HPβCD complexes were less stable than their unsubstituted counterparts. This indicates that increased hydrophobic contacts are not always accompanied by increased binding strength. The linear dependence of ΔC p °, ΔH° and ΔS° on the number of HP-chains give rise to isoentropic and isoenthalpic temperatures at which ΔH° and ΔS° are independent of the number of HP-chains on the host CD (but depend on the type of bile salt). Interestingly, these convergence temperatures are close to what is observed for unfolding of proteins and may be a common feature of hydrophobic dehydration",
    author = "Sch{\"o}nbeck, {Jens Christian Sidney} and Rene Holm and Peter Westh and Peters, {G{\"u}nther H.}",
    year = "2014",
    doi = "10.1007/s10847-013-0305-2",
    language = "English",
    volume = "78",
    pages = "351--361",
    journal = "Journal of Inclusion Phenomena and Macrocyclic Chemistry",
    issn = "1388-3127",
    publisher = "Springer Netherlands",
    number = "1-4",

    }

    Extending the hydrophobic cavity of beta-cyclodextrin results in more negative heat capacity changes but reduced binding affinities. / Schönbeck, Jens Christian Sidney; Holm, Rene; Westh, Peter; Peters, Günther H.

    I: Journal of Inclusion Phenomena and Macrocyclic Chemistry, Bind 78, Nr. 1-4, 2014, s. 351-361.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Extending the hydrophobic cavity of beta-cyclodextrin results in more negative heat capacity changes but reduced binding affinities

    AU - Schönbeck, Jens Christian Sidney

    AU - Holm, Rene

    AU - Westh, Peter

    AU - Peters, Günther H.

    PY - 2014

    Y1 - 2014

    N2 - The formation of inclusion complexes of hydroxypropylated β-cyclodextrins (CDs) with three bile salts are investigated to shed light on the role played by the hydroxypropyl (HP) substituents. The HP-chains are situated at the rim of the CD and may thus extend the hydrophobic cavity of the CD. Calorimetric titrations in a broad temperature range and molecular dynamics simulations confirm previous speculations that the HP-chains cause an increase in dehydrated nonpolar surface area upon formation of the complexes. This additional burial of nonpolar surface area, 12–16 Å2 per HP-chain according to the MD simulations, results in more negative values of ΔC p °, which are in quantitative agreement with what is expected for hydrophobic dehydration. Although these observations support the picture of an extended hydrophobic cavity, HPβCD complexes were less stable than their unsubstituted counterparts. This indicates that increased hydrophobic contacts are not always accompanied by increased binding strength. The linear dependence of ΔC p °, ΔH° and ΔS° on the number of HP-chains give rise to isoentropic and isoenthalpic temperatures at which ΔH° and ΔS° are independent of the number of HP-chains on the host CD (but depend on the type of bile salt). Interestingly, these convergence temperatures are close to what is observed for unfolding of proteins and may be a common feature of hydrophobic dehydration

    AB - The formation of inclusion complexes of hydroxypropylated β-cyclodextrins (CDs) with three bile salts are investigated to shed light on the role played by the hydroxypropyl (HP) substituents. The HP-chains are situated at the rim of the CD and may thus extend the hydrophobic cavity of the CD. Calorimetric titrations in a broad temperature range and molecular dynamics simulations confirm previous speculations that the HP-chains cause an increase in dehydrated nonpolar surface area upon formation of the complexes. This additional burial of nonpolar surface area, 12–16 Å2 per HP-chain according to the MD simulations, results in more negative values of ΔC p °, which are in quantitative agreement with what is expected for hydrophobic dehydration. Although these observations support the picture of an extended hydrophobic cavity, HPβCD complexes were less stable than their unsubstituted counterparts. This indicates that increased hydrophobic contacts are not always accompanied by increased binding strength. The linear dependence of ΔC p °, ΔH° and ΔS° on the number of HP-chains give rise to isoentropic and isoenthalpic temperatures at which ΔH° and ΔS° are independent of the number of HP-chains on the host CD (but depend on the type of bile salt). Interestingly, these convergence temperatures are close to what is observed for unfolding of proteins and may be a common feature of hydrophobic dehydration

    U2 - 10.1007/s10847-013-0305-2

    DO - 10.1007/s10847-013-0305-2

    M3 - Journal article

    VL - 78

    SP - 351

    EP - 361

    JO - Journal of Inclusion Phenomena and Macrocyclic Chemistry

    JF - Journal of Inclusion Phenomena and Macrocyclic Chemistry

    SN - 1388-3127

    IS - 1-4

    ER -