title: Synthesis and protein degradation capacity of photoactivated enediynes.
abstract: [structure: see text] The viability of proteins as targets of thermally and photoactivated enediynes has been confirmed at the molecular level. Model studies using a labeled substrate confirmed the efficacy of atom transfer from diyl radicals produced from enediynes to form captodatively stabilized carbon centered aminoacyl radicals, which then undergo either fragmentation or dimerization. To exploit this finding, a family of enediynes was developed using an intramolecular coupling strategy. Derivatives were prepared and used to target specific proteins, showing good correlation between affinity and photoinduced protein degrading activity. The findings have potential applications in the design of artificial chemical proteases and add to our understanding of the mechanism of action of the clinically important enediyne antitumor antibiotics.
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts, 02115, USA.
authors.forename: Farid S
authors.initials: FS
authors.lastname: Fouad
authors.forename: Justin M
authors.initials: JM
authors.lastname: Wright
authors.forename: Gary
authors.initials: G
authors.lastname: Plourde
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Purohit
authors.forename: Justin K
authors.initials: JK
authors.lastname: Wyatt
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Shafey
authors.forename: George
authors.initials: G
authors.lastname: Hynd
authors.forename: Curtis F
authors.initials: CF
authors.lastname: Crasto
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Lin
authors.forename: Graham B
authors.initials: GB
authors.lastname: Jones
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D006801:Humans; D015394:Molecular Structure; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism; D010777:Photochemistry; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000528:radiation effects; D011960:Receptors, Estrogen / Q000737:chemistry* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D000480:Alkynes; D017319:Photosensitizing Agents; D011960:Receptors, Estrogen; D012710:Serum Albumin, Bovine; D009113:Muramidase