Identification of Novel Inhibitors That Disrupt STAT3-DNA Interaction from a γ-AApeptide OBOC Combinatorial Library

Overview

Journal Chem Commun (Camb)

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2014 Jun 26

PMID 24964402

Citations 11

Authors

Peng Teng

Xiaolei Zhang

Haifan Wu

Qiao Qiao

Said M Sebti

Jianfeng Cai

Affiliations

Soon will be listed here.

Abstract

From a γ-AApeptide-based one-bead-one-compound (OBOC) combinatorial library, we identified γ-AApeptides that can selectively inhibit STAT3-DNA interaction and suppress the expression levels of STAT3 target genes in intact cells. Our results demonstrate that in addition to the SH2 domain, the DNA binding domain of STAT3 is targetable for the development of a new generation of anti-cancer therapeutics.

Citing Articles

The folding propensity of α/sulfono-γ-AA peptidic foldamers with both left- and right-handedness.

Teng P, Zheng M, Cerrato D, Shi Y, Zhou M, Xue S Commun Chem. 2023; 4(1):58.

PMID: 36697518 PMC: 9814141. DOI: 10.1038/s42004-021-00496-0.

Rational Design of Right-Handed Heterogeneous Peptidomimetics as Inhibitors of Protein-Protein Interactions.

Shi Y, Sang P, Lu J, Higbee P, Chen L, Yang L J Med Chem. 2020; 63(21):13187-13196.

PMID: 33140956 PMC: 8170677. DOI: 10.1021/acs.jmedchem.0c01638.

Aggregation-Induced Emissive and Circularly Polarized Homogeneous Sulfono-γ-AApeptide Foldamers.

Shi Y, Sang P, Yin G, Gao R, Liang X, Brzozowski R Adv Opt Mater. 2020; 8(14).

PMID: 33072491 PMC: 7567131. DOI: 10.1002/adom.201902122.

γ-AApeptides-based Small Molecule Ligands That Disaggregate Human Islet Amyloid Polypeptide.

Bolarinwa O, Li C, Khadka N, Li Q, Wang Y, Pan J Sci Rep. 2020; 10(1):95.

PMID: 31919432 PMC: 6952368. DOI: 10.1038/s41598-019-56500-0.

Stabilization of lncRNA GAS5 by a Small Molecule and Its Implications in Diabetic Adipocytes.

Shi Y, Parag S, Patel R, Lui A, Murr M, Cai J Cell Chem Biol. 2019; 26(3):319-330.e6.

PMID: 30661991 PMC: 10498384. DOI: 10.1016/j.chembiol.2018.11.012.

References

Page B, Ball D, Gunning P . Signal transducer and activator of transcription 3 inhibitors: a patent review. Expert Opin Ther Pat. 2010; 21(1):65-83. DOI: 10.1517/13543776.2011.539205. View

Lavecchia A, Di Giovanni C, Cerchia C . Novel inhibitors of signal transducer and activator of transcription 3 signaling pathway: an update on the recent patent literature. Expert Opin Ther Pat. 2014; 24(4):383-400. DOI: 10.1517/13543776.2014.877443. View

Mandal P, Liao W, McMurray J . Synthesis of phosphatase-stable, cell-permeable peptidomimetic prodrugs that target the SH2 domain of Stat3. Org Lett. 2009; 11(15):3394-7. PMC: 2836187. DOI: 10.1021/ol9012662. View

Cheng F, Wang H, Horna P, Wang Z, Shah B, Sahakian E . Stat3 inhibition augments the immunogenicity of B-cell lymphoma cells, leading to effective antitumor immunity. Cancer Res. 2012; 72(17):4440-8. PMC: 3990429. DOI: 10.1158/0008-5472.CAN-11-3619. View

Urlam M, Pireddu R, Ge Y, Zhang X, Sun Y, Lawrence H . Development of new -Arylbenzamides as STAT3 Dimerization Inhibitors. Medchemcomm. 2013; 4(6):932-941. PMC: 3780559. DOI: 10.1039/C3MD20323A. View

Zhang X, Sun Y, Pireddu R, Yang H, Urlam M, Lawrence H . A novel inhibitor of STAT3 homodimerization selectively suppresses STAT3 activity and malignant transformation. Cancer Res. 2013; 73(6):1922-33. PMC: 4030628. DOI: 10.1158/0008-5472.CAN-12-3175. View

Niu Y, Padhee S, Wu H, Bai G, Harrington L, Burda W . Identification of γ-AApeptides with potent and broad-spectrum antimicrobial activity. Chem Commun (Camb). 2011; 47(44):12197-12199. PMC: 3746764. DOI: 10.1039/c1cc14476f. View

Gomika Udugamasooriya D, Dineen S, Brekken R, Kodadek T . A peptoid "antibody surrogate" that antagonizes VEGF receptor 2 activity. J Am Chem Soc. 2008; 130(17):5744-52. DOI: 10.1021/ja711193x. View

Mandal P, Ren Z, Chen X, Kaluarachchi K, Liao W, McMurray J . Structure-Activity Studies of Phosphopeptidomimetic Prodrugs Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3 (Stat3). Int J Pept Res Ther. 2014; 19(1):3-12. PMC: 3974845. DOI: 10.1007/s10989-012-9313-0. View

10.

Ren Z, Cabell L, Schaefer T, McMurray J . Identification of a high-affinity phosphopeptide inhibitor of Stat3. Bioorg Med Chem Lett. 2003; 13(4):633-6. DOI: 10.1016/s0960-894x(02)01050-8. View

11.

Fletcher S, Page B, Zhang X, Yue P, Li Z, Sharmeen S . Antagonism of the Stat3-Stat3 protein dimer with salicylic acid based small molecules. ChemMedChem. 2011; 6(8):1459-70. PMC: 3192013. DOI: 10.1002/cmdc.201100194. View

12.

Gunning P, Glenn M, Siddiquee K, Katt W, Masson E, Sebti S . Targeting protein-protein interactions: suppression of Stat3 dimerization with rationally designed small-molecule, nonpeptidic SH2 domain binders. Chembiochem. 2008; 9(17):2800-3. PMC: 2728599. DOI: 10.1002/cbic.200800291. View

13.

Buettner R, Corzano R, Rashid R, Lin J, Senthil M, Hedvat M . Alkylation of cysteine 468 in Stat3 defines a novel site for therapeutic development. ACS Chem Biol. 2011; 6(5):432-43. PMC: 3098940. DOI: 10.1021/cb100253e. View

14.

Yang Y, Niu Y, Hong H, Wu H, Zhang Y, Engle J . Radiolabeled γ-AApeptides: a new class of tracers for positron emission tomography. Chem Commun (Camb). 2012; 48(63):7850-2. PMC: 3397393. DOI: 10.1039/c2cc33620k. View

15.

Masciocchi D, Gelain A, Villa S, Meneghetti F, Barlocco D . Signal transducer and activator of transcription 3 (STAT3): a promising target for anticancer therapy. Future Med Chem. 2011; 3(5):567-97. DOI: 10.4155/fmc.11.22. View

16.

Aquino C, Sarkar M, Chalmers M, Mendes K, Kodadek T, Micalizio G . A biomimetic polyketide-inspired approach to small-molecule ligand discovery. Nat Chem. 2012; 4(2):99-104. PMC: 3266625. DOI: 10.1038/nchem.1200. View

17.

Zhang X, Yue P, Page B, Li T, Zhao W, Namanja A . Orally bioavailable small-molecule inhibitor of transcription factor Stat3 regresses human breast and lung cancer xenografts. Proc Natl Acad Sci U S A. 2012; 109(24):9623-8. PMC: 3386073. DOI: 10.1073/pnas.1121606109. View

18.

Li Y, Smith C, Wu H, Padhee S, Manoj N, Cardiello J . Lipidated cyclic γ-AApeptides display both antimicrobial and anti-inflammatory activity. ACS Chem Biol. 2013; 9(1):211-7. PMC: 3947011. DOI: 10.1021/cb4006613. View

19.

Mandal P, Gao F, Lu Z, Ren Z, Ramesh R, Birtwistle J . Potent and selective phosphopeptide mimetic prodrugs targeted to the Src homology 2 (SH2) domain of signal transducer and activator of transcription 3. J Med Chem. 2011; 54(10):3549-63. PMC: 3319156. DOI: 10.1021/jm2000882. View

20.

Siddiquee K, Gunning P, Glenn M, Katt W, Zhang S, Schrock C . An oxazole-based small-molecule Stat3 inhibitor modulates Stat3 stability and processing and induces antitumor cell effects. ACS Chem Biol. 2007; 2(12):787-98. DOI: 10.1021/cb7001973. View