title: Synthesis and biological evaluation of open-chain analogs of cyclic peptides as inhibitors of cellular Shp2 activity.
abstract: A series of open-chain analogs of cyclic peptides was designed and synthesized using sansalvamide A as a model compound. All compounds exhibited low antitumor activity. Furthermore, the evaluation of their inhibitory potency toward IMPDH, SHP2, ACHE, proteasome, MAGL, and cathepsin B showed that all of the compounds were potent against protein tyrosine phosphatase Shp2. Specifically, compounds 1a, 1d, 2b, and 2f were found to inhibit SHP2 with IC50 values in the low micromolar range and good selectivity. Based on the molecular docking results, the binding modes of the chain cyclic peptides in the active center of SHP2 were discussed.
authors: College of Sciences, Hebei University of Science & Technology, Shijiazhuang 050018, People's Republic of China.
authors: Xiao-Li
authors: XL
authors: Zhen
authors: College of Sciences, Hebei University of Science & Technology, Shijiazhuang 050018, People's Republic of China.
authors: Wen-Hui
authors: WH
authors: Yin
authors: College of Sciences, Hebei University of Science & Technology, Shijiazhuang 050018, People's Republic of China.
authors: Xia
authors: X
authors: Tian
authors: College of Sciences, Hebei University of Science & Technology, Shijiazhuang 050018, People's Republic of China.
authors: Zhen-Jie
authors: ZJ
authors: Ma
authors: College of Chemical & Pharmaceutical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, People's Republic of China.
authors: Shi-Ming
authors: SM
authors: Fan
authors: College of Sciences, Hebei University of Science & Technology, Shijiazhuang 050018, People's Republic of China. Electronic address: han_jianrong@126.com.
authors: Jian-Rong
authors: JR
authors: Han
authors: College of Chemical & Pharmaceutical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, People's Republic of China. Electronic address: chlsx@hebust.edu.cnt.
authors: Shouxin
authors: S
authors: Liu
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry; D020134:Catalytic Domain; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000737:chemistry; D007700:Kinetics; D062105:Molecular Docking Simulation; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D058851:GPI-Linked Proteins; D010456:Peptides, Cyclic; D007168:IMP Dehydrogenase; C488211:IMPDH1 protein, human; C548244:ACHE protein, human; D000110:Acetylcholinesterase; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D002401:Cathepsin B; D046988:Proteasome Endopeptidase Complex
keywords: Chain peptides; Inhibitory activity; Molecular docking; SHP2; Synthesis