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Recognition of ASF1 by Using Hydrocarbon-Constrained Peptides.

ABSTRACT: Inhibiting the histone H3-ASF1 (anti-silencing function?1) protein-protein interaction (PPI) represents a potential approach for treating numerous cancers. As an ?-helix-mediated PPI, constraining the key histone H3 helix (residues 118-135) is a strategy through which chemical probes might be elaborated to test this hypothesis. In this work, variant H3118-135 peptides bearing pentenylglycine residues at the i and i+4 positions were constrained by olefin metathesis. Biophysical analyses revealed that promotion of a bioactive helical conformation depends on the position at which the constraint is introduced, but that the potency of binding towards ASF1 is unaffected by the constraint and instead that enthalpy-entropy compensation occurs.

SUBMITTER: Bakail M

PROVIDER: S-EPMC6468270 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Recognition of ASF1 by Using Hydrocarbon-Constrained Peptides.

Bakail May M Rodriguez-Marin Silvia S Hegedüs Zsófia Z Perrin Marie E ME Ochsenbein Françoise F Wilson Andrew J AJ

Chembiochem : a European journal of chemical biology 20190213 7

Inhibiting the histone H3-ASF1 (anti-silencing function 1) protein-protein interaction (PPI) represents a potential approach for treating numerous cancers. As an α-helix-mediated PPI, constraining the key histone H3 helix (residues 118-135) is a strategy through which chemical probes might be elaborated to test this hypothesis. In this work, variant H3<sub>118-135</sub> peptides bearing pentenylglycine residues at the i and i+4 positions were constrained by olefin metathesis. Biophysical analyse ...[more]

PMID: 30512234

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