Potency of a small molecule that targets the molluscum contagiosum virus processivity factor increases when conjugated to a tripeptide.

Autor: Guan H; Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA., Nuth M; Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA., Scott RW; Fox Chase Therapeutics Discovery, Inc., USA., Parker MH; Fox Chase Therapeutics Discovery, Inc., USA., Strobel ED; Fox Chase Therapeutics Discovery, Inc., USA., Reitz AB; Fox Chase Therapeutics Discovery, Inc., USA., Kulp JL 3rd; Conifer Point Pharmaceuticals, Doylestown, PA, USA., Ricciardi RP; Department of Basic and Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA; Abramson Cancer Center, School of Medicine, University of Pennsylvania, USA. Electronic address: ricciard@upenn.edu.
Jazyk: angličtina
Zdroj: Antiviral research [Antiviral Res] 2024 Jun; Vol. 226, pp. 105899. Date of Electronic Publication: 2024 May 03.
DOI: 10.1016/j.antiviral.2024.105899
Abstrakt: We recently developed compound FC-7269 for targeting the Molluscum contagiosum virus processivity factor (mD4) and demonstrated its ability to inhibit viral processive DNA synthesis in vitro and cellular infection of an mD4-dependent virus (Antiviral Res 211, 2023,105520). However, despite a thorough medicinal chemistry campaign we were unable to generate a potent second analog as a requisite for drug development. We overcame this impasse, by conjugating a short hydrophobic trivaline peptide to FC-7269 to produce FC-TriVal-7269 which significantly increased antiviral potency and reduced cellular toxicity.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier B.V.)
Databáze: MEDLINE
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