title: Protein engineering strategies with potential applications for altering clinically relevant cellular pathways at the protein level.
abstract: All diseases can be fundamentally viewed as the result of malfunctioning cellular pathways. Protein engineering offers the potential to develop new tools that will allow these dysfunctional pathways to be better understood, in addition to potentially providing new routes to restore proper function. Here we discuss different approaches that can be used to change the intracellular activity of a protein by intervening at the protein level: targeted protein sequestration, protein recruitment, protein degradation, and selective inhibition of binding interfaces. The potential of each of these tools to be developed into effective therapeutic treatments will also be discussed, along with any major barriers that currently block their translation into the clinic.
authors.affiliation: a Department of Molecular Biophysics & Biochemistry , Yale University , New Haven , CT , USA.|b Department of Chemistry , Yale University , New Haven , CT , USA.|c Integrated Graduate Program in Physical and Engineering Biology , Yale University , New Haven , CT , USA.
authors.forename: Lynne
authors.initials: L
authors.lastname: Regan
authors.affiliation: a Department of Molecular Biophysics & Biochemistry , Yale University , New Haven , CT , USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hinrichsen
authors.forename: Curran
authors.initials: C
authors.lastname: Oi
mesh_terms: D006801:Humans; D053858:Metabolic Networks and Pathways; D058990:Molecular Targeted Therapy; D015202:Protein Engineering / Q000379:methods*; D011506:Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D011506:Proteins
keywords: Protein engineering; cellular pathways; pathway engineering; protein degradation; protein sequestration; protein therapeutics