Coordination complex SH2 domain proteomimetics: an alternative approach to disrupting oncogenic protein-protein interactions.
We report the first application of coordination complexes as functional proteomimetics of the Src homology 2 (SH2) phosphopeptide-binding domain. As a proof-of-concept, functionalized bis-dipicolylamine (BDPA) copper(ii) complexes are shown to disrupt oncogenic Stat3-Stat3 protein complexes and elicit promising anti-tumour activity.
Drewry
Joel A
JA
Department of Chemistry, University of Toronto, Toronto, Canada.
Fletcher
Steven
S
Yue
Peibin
P
Marushchak
Denys
D
Zhao
Wei
W
Sharmeen
Sumaiya
S
Zhang
Xiaolei
X
Schimmer
Aaron D
AD
Gradinaru
Claudiu
C
Turkson
James
J
Gunning
Patrick T
PT
D000588:Amines / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D066246:ErbB Receptors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D010848:Picolinic Acids / Q000737:chemistry; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D050796:STAT3 Transcription Factor / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
C501847:2,2'-dipicolylamine; D000588:Amines; D056831:Coordination Complexes; D010848:Picolinic Acids; D050796:STAT3 Transcription Factor; D003300:Copper; D066246:ErbB Receptors