In-Tether Chiral Center Induced Helical Peptide Modulators Target p53-MDM2/MDMX and Inhibit Tumor Growth in Stem-Like Cancer Cell: Erratum

Hu, Kuan; Yin, Feng; Yu, Mengyin; Sun, Chengjie; Li, Jingxu; Liang, Yujie; Li, Wenjun; Xie, Ming‐Sheng; Lao, Yuanzhi; Liang, Wei; Li, Zigang

doi:10.7150/thno.31152

Cited by 2 publications

(2 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cysteine is lowly abundant and with unique reactivity, which makes it the most used residue for protein modification [43–48] . Peptide modulators provide a streamlined approach for interrupting PPIs [49–51] . We recently developed a peptide cyclization strategy via bis‐alkylation between Cys and Met.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Selective Covalent Targeting of Anti‐apoptotic BFL‐1 by a Sulfonium‐Tethered Peptide

et al. 2020

Self Cite

View full text Add to dashboard Cite

Anti-apoptotic B cell lymphoma 2 (BCL-2) family proteins are proven targets for human cancers. Targeting the BH3-binding pockets of these anti-apoptotic proteins could reactivate apoptosis in BCL-2-depedent cancers. BFL-1 is a BCL-2 family protein overexpressed in various chemoresistant cancers. A unique cysteine at the binding interface of the BH3 and BFL-1 was previously proven to be an intriguing targeting site to irreversibly inhibit BFL-1 functions with stabilized cyclic peptide bearing a covalent warhead. Recently, we developed a sulfonium-tethered peptide cyclization strategy to construct peptide ligands that could selectively and efficiently react with the cysteine(s) of target proteins near the interacting interface. Using this method, we constructed a BFL-1 peptide inhibitor, B4-MC, that could selectively conjugate with BFL-1 both in vitro and in cell. B4-MC showed good cellular uptake, colocalized with BFL-1 on mitochondria, and showed obvious growth inhibition of BFL-1 over-expressed cancer cell lines.

show abstract

Section: Methodsmentioning

confidence: 99%

“…[43][44][45][46][47][48] Peptide modulators provide a streamlined approach for interrupting PPIs. [49][50][51] We recently developed a peptide cyclization strategy via bis-alkylation between Cys and Met. Peptides with tunable tethers and an on-tether sulfonium center could be easily constructed.…”

mentioning

confidence: 99%

Selective Covalent Targeting of Anti‐apoptotic BFL‐1 by a Sulfonium‐Tethered Peptide

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Stabilized Peptide HDAC Inhibitors Derived from HDAC1 Substrate H3K56 for the Treatment of Cancer Stem–Like Cells In Vivo

Wang

Zhao

et al. 2019

Cancer Research

Self Cite

View full text Add to dashboard Cite

FDA-approved HDAC inhibitors exhibit dose-limiting adverse effects; thus, we sought to improve the therapeutic windows for this class of drugs. In this report, we describe a new class of peptide-based HDAC inhibitors derived from the HDAC1-specific substrate H3K56 with improved nonspecific toxicity compared with traditional small-molecular inhibitors. We showed that our designed peptides exerted superior antiproliferation effects on cancer stem–like cells with minimal toxicity to normal cells compared with the small-molecular inhibitor SAHA, which showed nonspecific toxicity to normal and cancer cells. These peptide inhibitors also inactivated cellular HDAC1 and HDAC6 and disrupted the formation of the HDAC1, LSD1, and CoREST complex. In ovarian teratocarcinoma (PA-1) and testicular embryonic carcinoma (NTERA-2) cell xenograft animal models (5 mice/group, 50 mg/kg, every other day, intraperitoneal injection), these peptides inhibited tumor growth by 80% to 90% with negligible organ (heart, liver, spleen, lung, kidney, brain) lesions. These results represent the first attempt to design chemically stabilized peptide inhibitors to investigate HDAC inhibition in cancer stem–like cells. These novel peptide inhibitors have significantly enhanced therapeutic window and offer promising opportunities for cancer therapy. Significance: Selective antiproliferative effects of stabilized peptide HDAC inhibitors toward cancer stem–like cells provide a therapeutic alternative that avoids high nonspecific toxicity of current drugs.

show abstract

In-Tether Chiral Center Induced Helical Peptide Modulators Target p53-MDM2/MDMX and Inhibit Tumor Growth in Stem-Like Cancer Cell: Erratum

Cited by 2 publications

References 1 publication

Selective Covalent Targeting of Anti‐apoptotic BFL‐1 by a Sulfonium‐Tethered Peptide

Selective Covalent Targeting of Anti‐apoptotic BFL‐1 by a Sulfonium‐Tethered Peptide

Stabilized Peptide HDAC Inhibitors Derived from HDAC1 Substrate H3K56 for the Treatment of Cancer Stem–Like Cells In Vivo

Contact Info

Product

Resources

About