title: Therapeutic Potential of Foldamers: From Chemical Biology Tools To Drug Candidates?
abstract: Over the past decade, foldamers have progressively emerged as useful architectures to mimic secondary structures of proteins. Peptidic foldamers, consisting of various amino acid based backbones, have been the most studied from a therapeutic perspective, while polyaromatic foldamers have barely evolved from their nascency and remain perplexing for medicinal chemists due to their poor drug-like nature. Despite these limitations, this compound class may still offer opportunities to study challenging targets or provide chemical biology tools. The potential of foldamer drug candidates reaching the clinic is still a stretch. Nevertheless, advances in the field have demonstrated their potential for the discovery of next generation therapeutics. In this perspective, the current knowledge of foldamers is reviewed in a drug discovery context. Recent advances in the early phases of drug discovery including hit finding, target validation, and optimization and molecular modeling are discussed. In addition, challenges and focus areas are debated and gaps highlighted.
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca , Pepparedsleden 1, Mölndal, 431 83, Sweden.|AstraZeneca MPI Satellite Unit, Department of Chemical Biology, Max Planck Institute of Molecular Physiology , Dortmund 44202, Germany.
authors.forename: Ranganath
authors.initials: R
authors.lastname: Gopalakrishnan
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca , Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: Andrey I
authors.initials: AI
authors.lastname: Frolov
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca , Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: Laurent
authors.initials: L
authors.lastname: Knerr
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca , Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: William J
authors.initials: WJ
authors.lastname: Drury
authors.affiliation: Cardiovascular and Metabolic Diseases, Innovative Medicines and Early Development Biotech Unit, AstraZeneca , Pepparedsleden 1, Mölndal, 431 83, Sweden.
authors.forename: Eric
authors.initials: E
authors.lastname: Valeur
mesh_terms: D055808:Drug Discovery; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017510:Protein Folding / Q000187:drug effects*
chemical_list: D010455:Peptides; D011084:Polycyclic Aromatic Hydrocarbons