Disrupting protein-protein interactions with non-peptidic, small molecule alpha-helix mimetics.
Many biological processes are regulated by protein-protein interactions (PPIs) and as such their misregulation can cause a multitude of diseases. Often the interactions between large proteins are mediated by small protein secondary structural domains, which project a minimum number of specifically arranged residues into the complementary surface of an interacting protein. Nature has the advantage of time, and over time has optimized those secondary structures, such as alpha-helices, beta-sheets and beta-strands, found at the interfaces of PPIs. Inspired by Nature's extensive optimization, chemists have used these secondary structures as templates in the design of small molecules that may act as structural and functional mimics of large rhenylogically organized protein secondary structures. Herein recent applications of the indane, terphenyl, terphenyl-inspired templates, polycyclic ether and benzodiazepinedione scaffolds, as non-peptidic, small molecule alpha-helix mimetics, to disrupt PPIs are detailed.
Cummings
Christopher G
CG
Department of Chemistry, Yale University, 225 Prospect Street, P.O. Box 208107, New Haven, CT 06520-8107, USA.
Hamilton
Andrew D
AD
D001570:Benzodiazepinones / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry; D007189:Indans / Q000737:chemistry; D025941:Protein Interaction Mapping / Q000379:methods*; D054852:Small Molecule Libraries / Q000737:chemistry*; D013730:Terphenyl Compounds / Q000737:chemistry
D001570:Benzodiazepinones; D004988:Ethers, Cyclic; D007189:Indans; D054852:Small Molecule Libraries; D013730:Terphenyl Compounds