Abstract:
:Binding of indoloquinolines with different aliphatic side chains to a parallel G-quadruplex derived from the MYC promoter sequence was characterized by optical and calorimetric measurements. ITC experiments performed at different temperatures enabled the determination of molar heat capacity changes upon quadruplex binding and a partitioning of the total binding free enthalpy into contributing terms with hydrophobic effects being major driving forces for all derivatives. Whereas affinities increase for indoloquinolines equipped with a long and positively charged side arm, the highest contribution of specific intermolecular interactions anticipated to impart enhanced specificity is found for a ligand with an uncharged ether aliphatic tail. Obtained thermodynamic signatures may considerably aid in the rational selection of ligand side chains for G-quadruplex binders with enhanced affinity or selectivity.
journal_name
Biochimiejournal_title
Biochimieauthors
Funke A,Weisz Kdoi
10.1016/j.biochi.2018.11.015subject
Has Abstractpub_date
2019-02-01 00:00:00pages
142-148eissn
0300-9084issn
1638-6183pii
S0300-9084(18)30340-7journal_volume
157pub_type
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