A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Systematic Study of Heteroarene Stacking Using a Congeneric Set of Molecular Glues for Procaspase-6
Tekijät: Togo Takaya, Tram Linh, Denton Laura G., ElHilali-Pollard Xochina, Gu Jun, Jiang Jinglei, Liu Chenglei, Zhao Yan, Zhao Yanlong, Zheng Yinzhe, Zheng Yunping, Yang Jingjing, Fan Panpan, Arkin Michelle R., Härmä Harri, Sun Deqian, Canan Stacie S., Wheeler Steven E., Renslo Adam R.
Kustantaja: AMER CHEMICAL SOC
Julkaisuvuosi: 2023
Journal: Journal of Medicinal Chemistry
Tietokannassa oleva lehden nimi: JOURNAL OF MEDICINAL CHEMISTRY
Lehden akronyymi: J MED CHEM
Vuosikerta: 66
Numero: 14
Aloitussivu: 9784
Lopetussivu: 9796
Sivujen määrä: 13
ISSN: 0022-2623
eISSN: 1520-4804
DOI: https://doi.org/10.1021/acs.jmedchem.3c00590
Verkko-osoite: https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.3c00590
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/180392842
Heteroaromatic stacking interactions are important indrug binding,supramolecular chemistry, and materials science, making protein-ligandmodel systems of these interactions of considerable interest. Herewe studied 30 congeneric ligands that each present a distinct heteroarenefor stacking between tyrosine residues at the dimer interface of procaspase-6.Complex X-ray crystal structures of 10 analogs showed that stackinggeometries were well conserved, while high-accuracy computations showedthat heteroarene stacking energy was well correlated with predictedoverall ligand binding energies. Empirically determined K (D) values in this system thus provide a useful measureof heteroarene stacking with tyrosine. Stacking energies are discussedin the context of torsional strain, the number and positioning ofheteroatoms, tautomeric state, and coaxial orientation of heteroarenein the stack. Overall, this study provides an extensive data set ofempirical and high-level computed binding energies in a versatilenew protein-ligand system amenable to studies of other intermolecularinteractions.
Ladattava julkaisu This is an electronic reprint of the original article. |  |
