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Current Protein & Peptide Science

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ISSN (Print): 1389-2037
ISSN (Online): 1875-5550

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Research Article

Reduced Level of Prolylhydroxyproline in the Nail Clippings of Oral Cancer Patients and its Role as an Activator of Phospholipase C-β2

Author(s): Devyani Bhatkar, Dipti Nimburkar, Ajay Kumar Raj, Kiran B. Lokhande, Kratika Khunteta, Haet Kothari, Mrudula Joshi, Sachin C. Sarode and Nilesh Kumar Sharma*

Volume 24, Issue 8, 2023

Published on: 22 August, 2023

Page: [684 - 699] Pages: 16

DOI: 10.2174/1389203724666230810094615

Price: $65

Abstract

Background: The oral cancer microenvironment plays an important role in the development and progression of the disease which depicts the heterogeneous nature of diseases. Several cellular and non-cellular factors, including dipeptides, have been reported to drive tumor progression and metastasis. Among various secreted molecules in the tumor microenvironment, prolylhydroxyproline (Pro-Hyp) is a collagen-degraded product with specific relevance to fibrosis and oral cancer. However, the detection of Pro-Hyp in the nails of oral cancer patients is a potential biomarker, and our understanding of the biological relevance of Pro-Hyp is highly limited.

Methods: Here, the authors have attempted to use a novel and in-house vertical tube gel electrophoresis (VTGE) protocol to evaluate the level of Pro-Hyp in the nails of oral cancer patients and healthy subjects. Furthermore, we employed molecular docking and molecular dynamics (MD) simulations to predict the biological function of Pro-Hyp. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp and a known PLC-β2 activator, m-3M3FBS, were evaluated by the SWISS-ADME server.

Results: We report that among various key metabolites, Pro-Hyp, a dipeptide, is reduced in the nails of oral cancer patients. Molecular docking and MD simulations helped to suggest the potential role of Pro-Hyp as an activator of Phospholipase C-β2 (PLC-β2). Pro-Hyp displayed good binding affinity (-7.6 kcal/mol) with specific interactions by a conventional hydrogen bond with key residues, such as HIS311, HIS312, VAL641, and GLU743. MD simulations showed that the activator binding residues and stability of complexes are similar to the well-known activator m-3M3FBS of PLC-β2. ADME profiles such as the druglikeness and leadlikeness of Pro-Hyp were found to be highly comparable and even better than those of m-3M3FBS.

Conclusion: This study is one of the first reports on Pro-Hyp as a metabolite biomarker in the nails of oral cancer patients. Furthermore, the implications of Pro-Hyp are proposed to activate PLC-β2 as a pro-tumor signaling cascade. In the future, diagnostic and therapeutic approaches may be explored as biomarkers and mimetic of Pro-Hyp.

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[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Gadbail, A.R.; Chaudhary, M.; Gawande, M.; Hande, A.; Sarode, S.; Tekade, S.A.; Korde, S.; Zade, P.; Bhowate, R.; Borle, R.; Patil, S. Oral squamous cell carcinoma in the background of oral submucous fibrosis is a distinct clinicopathological entity with better prognosis. J. Oral Pathol. Med., 2017, 46(6), 448-453.
[http://dx.doi.org/10.1111/jop.12553] [PMID: 28129456]
[3]
Jeng, J.H.; Chang, M.C.; Hahn, L.J. Role of areca nut in betel quid-associated chemical carcinogenesis: current awareness and future perspectives. Oral Oncol., 2001, 37(6), 477-492.
[http://dx.doi.org/10.1016/S1368-8375(01)00003-3] [PMID: 11435174]
[4]
Tilakaratne, W.M.; Klinikowski, M.F.; Saku, T.; Peters, T.J.; Warnakulasuriya, S. Oral submucous fibrosis: Review on aetiology and pathogenesis. Oral Oncol., 2006, 42(6), 561-568.
[http://dx.doi.org/10.1016/j.oraloncology.2005.08.005] [PMID: 16311067]
[5]
Li, W.C.; Lee, P.L.; Chou, I.C.; Chang, W.J.; Lin, S.C.; Chang, K.W. Molecular and cellular cues of diet-associated oral carcinogenesis-with an emphasis on areca-nut-induced oral cancer development. J. Oral Pathol. Med., 2015, 44(3), 167-177.
[http://dx.doi.org/10.1111/jop.12171] [PMID: 24527773]
[6]
Cheng, R.H.; Wang, Y.P.; Chang, J.Y.F.; Pan, Y.H.; Chang, M.C.; Jeng, J.H. Genetic susceptibility and protein expression of extracellular matrix turnover-related genes in oral submucous fibrosis. Int. J. Mol. Sci., 2020, 21(21), 8104.
[http://dx.doi.org/10.3390/ijms21218104] [PMID: 33143101]
[7]
Chaffer, C.L.; Weinberg, R.A. A perspective on cancer cell metastasis. Science, 2011, 331(6024), 1559-1564.
[http://dx.doi.org/10.1126/science.1203543] [PMID: 21436443]
[8]
Inoue, H.; Iguch, H.; Kouno, A.; Tsuruta, Y. Fluorometric determination of N-terminal prolyl dipeptides, proline and hydroxyproline in human serum by pre-column high-performance liquid chromatography using 4-(5,6-dimethoxy-2-phthalimidinyl)-2-methoxy- phenylsulfonyl chloride. J. Chromatogr., Biomed. Appl., 2001, 757(2), 369-373.
[http://dx.doi.org/10.1016/S0378-4347(01)00162-1] [PMID: 11417884]
[9]
Ala-aho, R.; Kähäri, V.M. Collagenases in cancer. Biochimie, 2005, 87(3-4), 273-286.
[http://dx.doi.org/10.1016/j.biochi.2004.12.009] [PMID: 15781314]
[10]
Shoulders, M.D.; Raines, R.T. Collagen structure and stability. Annu. Rev. Biochem., 2009, 78(1), 929-958.
[http://dx.doi.org/10.1146/annurev.biochem.77.032207.120833] [PMID: 19344236]
[11]
Wirtz, D.; Konstantopoulos, K.; Searson, P.C. The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat. Rev. Cancer, 2011, 11(7), 512-522.
[http://dx.doi.org/10.1038/nrc3080] [PMID: 21701513]
[12]
Gilkes, D.M.; Chaturvedi, P.; Bajpai, S.; Wong, C.C.; Wei, H.; Pitcairn, S.; Hubbi, M.E.; Wirtz, D.; Semenza, G.L. Collagen prolyl hydroxylases are essential for breast cancer metastasis. Cancer Res., 2013, 73(11), 3285-3296.
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3963] [PMID: 23539444]
[13]
Bonnans, C.; Chou, J.; Werb, Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol., 2014, 15(12), 786-801.
[http://dx.doi.org/10.1038/nrm3904] [PMID: 25415508]
[14]
Xiong, G.; Deng, L.; Zhu, J.; Rychahou, P.G.; Xu, R. Prolyl-4-hydroxylase α subunit 2 promotes breast cancer progression and metastasis by regulating collagen deposition. BMC Cancer, 2014, 14(1), 1.
[http://dx.doi.org/10.1186/1471-2407-14-1] [PMID: 24383403]
[15]
Lu, P.; Takai, K.; Weaver, V.M.; Werb, Z. Extracellular matrix degradation and remodeling in development and disease. Cold Spring Harb. Perspect. Biol., 2011, 3(12), a005058.
[http://dx.doi.org/10.1101/cshperspect.a005058] [PMID: 21917992]
[16]
Kimira, Y.; Odaira, H.; Nomura, K.; Taniuchi, Y.; Inoue, N.; Nakatani, S.; Shimizu, J.; Wada, M.; Mano, H. Collagen-derived dipeptide prolyl-hydroxyproline promotes osteogenic differentiation through Foxg1. Cell. Mol. Biol. Lett., 2017, 22(1), 27-27.
[http://dx.doi.org/10.1186/s11658-017-0060-2] [PMID: 29213293]
[17]
Sato, K.; Asai, T.T.; Jimi, S. Collagen-derived di-peptide, prolylhydroxyproline (Pro-Hyp): A new low molecular weight growth-initiating factor for specific fibroblasts associated with wound healing. Front. Cell Dev. Biol., 2020, 8, 548975.
[http://dx.doi.org/10.3389/fcell.2020.548975] [PMID: 33330443]
[18]
Mitruka, M.; Gore, C.R.; Kumar, A.; Sarode, S.C.; Sharma, N.K. Undetectable free aromatic amino acids in nails of breast carcinoma: Biomarker discovery by a novel metabolite purification VTGE system. Front. Oncol., 2020, 10, 908.
[http://dx.doi.org/10.3389/fonc.2020.00908] [PMID: 32695662]
[19]
Patel, R.; Raj, A.K.; Lokhande, K.B.; Almasri, M.A.; Alzahrani, K.J.; Almeslet, A.S.; Swamy, K.V.; Sarode, G.S.; Sarode, S.C.; Patil, S.; Sharma, N.K. Detection of nail oncometabolite SAICAR in oral cancer patients and its molecular interactions with PKM2 enzyme. Int. J. Environ. Res. Public Health, 2021, 18(21), 11225.
[http://dx.doi.org/10.3390/ijerph182111225] [PMID: 34769743]
[20]
Sharma, N.K.; Sarode, S.C.; Sarode, G.S.; Patil, S. Nail as a dump yard for drugs and their metabolites: Blessing in disguise for nail cancer? Med. Hypotheses, 2020, 142, 109744.
[http://dx.doi.org/10.1016/j.mehy.2020.109744] [PMID: 32334295]
[21]
Salcedo-Bellido, I.; Gutiérrez-González, E.; García-Esquinas, E.; Fernández de Larrea-Baz, N.; Navas-Acien, A.; Téllez-Plaza, M.; Pastor-Barriuso, R.; Lope, V.; Gómez-Ariza, J.L.; García-Barrera, T.; Pollán, M.; Jiménez Moleón, J.J.; Pérez-Gómez, B. Toxic metals in toenails as biomarkers of exposure: A review. Environ. Res., 2021, 197, 111028.
[http://dx.doi.org/10.1016/j.envres.2021.111028] [PMID: 33753073]
[22]
Miyake, T.; Minagawa, A.; Ito, S.; Yokokawa, Y.; Wakamatsu, K.; Okuyama, R. Utility of melanin degradation products in the nail for diagnosing nail apparatus melanoma. Acta Derm. Venereol., 2021, 101(2), adv00387.
[http://dx.doi.org/10.2340/00015555-3757] [PMID: 33521832]
[23]
Jaramillo Ortiz, S.; Howsam, M.; van Aken, E.H.; Delanghe, J.R.; Boulanger, E.; Tessier, F.J. Biomarkers of disease in human nails: A comprehensive review. Crit. Rev. Clin. Lab. Sci., 2022, 59(2), 125-141.
[http://dx.doi.org/10.1080/10408363.2021.1991882] [PMID: 34726550]
[24]
Washio, J.; Takahashi, N. Metabolomic Studies of oral biofilm, oral cancer, and beyond. Int. J. Mol. Sci., 2016, 17(6), 870.
[http://dx.doi.org/10.3390/ijms17060870] [PMID: 27271597]
[25]
Sridharan, G.; Ramani, P.; Patankar, S.; Vijayaraghavan, R. Evaluation of salivary metabolomics in oral leukoplakia and oral squamous cell carcinoma. J. Oral Pathol. Med., 2019, 48(4), 299-306.
[http://dx.doi.org/10.1111/jop.12835] [PMID: 30714209]
[26]
Grootveld, M.; Percival, B.C.; Page, G.; Hunwin, K.; Bhogadia, M.; Chan, W.; Edgar, M. Updates and original case studies focused on the nmr-linked metabolomics analysis of human oral fluids Part II: Applications to the diagnosis and prognostic monitoring of oral and systemic cancers. Metabolites., 2022, 12(9), 778.
[http://dx.doi.org/10.3390/metabo12090778] [PMID: 36144183]
[27]
Liu, W.; Ji, T.; Zhang, C.; Zhou, Q.; Bao, Z. Cell-free DNA hypermethylated genes may have a limited role in cancer screening but a potential role in risk assessment of head and neck cancer. Oral Oncol., 2022, 134, 106129.
[http://dx.doi.org/10.1016/j.oraloncology.2022.106129] [PMID: 36202068]
[28]
Wu, M.; Li, B.; Zhang, X.; Sun, G. Serum metabolomics reveals an innovative diagnostic model for salivary gland tumors. Anal. Biochem., 2022, 655, 114853.
[http://dx.doi.org/10.1016/j.ab.2022.114853] [PMID: 35970412]
[29]
Chen, H.C.; Chen, Y.Y.; Chao, M.R.; Chang, Y.Z. Validation of a high-throughput method for simultaneous determination of areca nut and tobacco biomarkers in hair using microwave-assisted extraction and isotope dilution liquid chromatography tandem mass spectrometry. J. Pharm. Biomed. Anal., 2022, 216, 114775.
[http://dx.doi.org/10.1016/j.jpba.2022.114775] [PMID: 35490505]
[30]
da Costa, N.L.; de Sá Alves, M.; de Sá Rodrigues, N.; Bandeira, C.M.; Oliveira Alves, M.G.; Mendes, M.A.; Cesar Alves, L.A.; Almeida, J.D.; Barbosa, R. Finding the combination of multiple biomarkers to diagnose oral squamous cell carcinoma – A data mining approach. Comput. Biol. Med., 2022, 143, 105296.
[http://dx.doi.org/10.1016/j.compbiomed.2022.105296] [PMID: 35149458]
[31]
Horowitz, L.F.; Hirdes, W.; Suh, B.C.; Hilgemann, D.W.; Mackie, K.; Hille, B. Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current. J. Gen. Physiol., 2005, 126(3), 243-262.
[http://dx.doi.org/10.1085/jgp.200509309] [PMID: 16129772]
[32]
Harden, T.K.; Sondek, J. Regulation of phospholipase C isozymes by ras superfamily GTPases. Annu. Rev. Pharmacol. Toxicol., 2006, 46(1), 355-379.
[http://dx.doi.org/10.1146/annurev.pharmtox.46.120604.141223] [PMID: 16402909]
[33]
Fiume, R.; Ramazzotti, G.; Teti, G.; Chiarini, F.; Faenza, I.; Mazzotti, G.; Billi, A.M.; Cocco, L. Involvement of nuclear PLCβl in lamin B1 phosphorylation and G2/M cell cycle progression. FASEB J., 2009, 23(3), 957-966.
[http://dx.doi.org/10.1096/fj.08-121244] [PMID: 19028838]
[34]
Lattanzio, R.; Piantelli, M.; Falasca, M. Role of phospholipase C in cell invasion and metastasis. Adv. Biol. Regul., 2013, 53(3), 309-318.
[http://dx.doi.org/10.1016/j.jbior.2013.07.006] [PMID: 23925006]
[35]
Lyon, A.M.; Tesmer, J.J.G. Structural insights into phospholipase C-β function. Mol. Pharmacol., 2013, 84(4), 488-500.
[http://dx.doi.org/10.1124/mol.113.087403] [PMID: 23880553]
[36]
Nakamura, Y.; Fukami, K. Regulation and physiological functions of mammalian phospholipase C. J. Biochem., 2017, 161(4), mvw094.
[http://dx.doi.org/10.1093/jb/mvw094] [PMID: 28130414]
[37]
Bae, Y.S.; Lee, T.G.; Park, J.C.; Hur, J.H.; Kim, Y.; Heo, K.; Kwak, J.Y.; Suh, P.G.; Ryu, S.H. Identification of a compound that directly stimulates phospholipase C activity. Mol. Pharmacol., 2003, 63(5), 1043-1050.
[http://dx.doi.org/10.1124/mol.63.5.1043] [PMID: 12695532]
[38]
Jezyk, M.R.; Snyder, J.T.; Gershberg, S.; Worthylake, D.K.; Harden, T.K.; Sondek, J. Crystal structure of Rac1 bound to its effector phospholipase C-β2. Nat. Struct. Mol. Biol., 2006, 13(12), 1135-1140.
[http://dx.doi.org/10.1038/nsmb1175] [PMID: 17115053]
[39]
Hicks, S.N.; Jezyk, M.R.; Gershburg, S.; Seifert, J.P.; Harden, T.K.; Sondek, J. General and versatile autoinhibition of PLC isozymes. Mol. Cell, 2008, 31(3), 383-394.
[http://dx.doi.org/10.1016/j.molcel.2008.06.018] [PMID: 18691970]
[40]
Wang, S.J.; Bourguignon, L.Y.W. Hyaluronan-CD44 promotes phospholipase C-mediated Ca2+ signaling and cisplatin resistance in head and neck cancer. Arch. Otolaryngol. Head Neck Surg., 2006, 132(1), 19-24.
[http://dx.doi.org/10.1001/archotol.132.1.19] [PMID: 16415424]
[41]
Bertagnolo, V.; Benedusi, M.; Brugnoli, F.; Lanuti, P.; Marchisio, M.; Querzoli, P.; Capitani, S. Phospholipase C-β2 promotes mitosis and migration of human breast cancer-derived cells. Carcinogenesis., 2007, 28(8), 1638-1645.
[http://dx.doi.org/10.1093/carcin/bgm078] [PMID: 17429106]
[42]
Jung, E.M.; Lee, T.J.; Park, J.W.; Bae, Y.S.; Kim, S.H.; Choi, Y.H.; Kwon, T.K. The novel phospholipase C activator, m-3M3FBS, induces apoptosis in tumor cells through caspase activation, down-regulation of XIAP and intracellular calcium signaling. Apoptosis., 2008, 13(1), 133-145.
[http://dx.doi.org/10.1007/s10495-007-0159-4] [PMID: 18060503]
[43]
Ma, L.W.; Zhou, Z.T.; He, Q.B.; Jiang, W.W. Phospholipase C-γ1 expression correlated with cancer progression of potentially malignant oral lesions. J. Oral Pathol. Med., 2013, 42(1), 47-52.
[http://dx.doi.org/10.1111/j.1600-0714.2012.01179.x] [PMID: 22671975]
[44]
Jiang, Y.; Liao, L.; Shrestha, C.; Ji, S.; Chen, Y.; Peng, J.; Wang, L.; Liao, E.; Xie, Z. Reduced expression of E-cadherin and p120-catenin and elevated expression of PLC-γ1 and PIKE are associated with aggressiveness of oral squamous cell carcinoma. Int. J. Clin. Exp. Pathol., 2015, 8(8), 9042-9051.
[PMID: 26464646]
[45]
Xiao, W.; Hong, H.; Kawakami, Y.; Kato, Y.; Wu, D.; Yasudo, H.; Kimura, A.; Kubagawa, H.; Bertoli, L.F.; Davis, R.S.; Chau, L.A.; Madrenas, J.; Hsia, C.C.; Xenocostas, A.; Kipps, T.J.; Hennighausen, L.; Iwama, A.; Nakauchi, H.; Kawakami, T. Tumor suppression by phospholipase C-beta3 via SHP-1-mediated dephosphorylation of Stat5. Cancer Cell., 2009, 16(2), 161-171.
[http://dx.doi.org/10.1016/j.ccr.2009.05.018] [PMID: 19647226]
[46]
Zuo, H.; Wong, Y.H. Association of activated Gαq to the tumor suppressor Fhit is enhanced by phospholipase Cβ. BMC Cancer, 2015, 15(1), 775.
[http://dx.doi.org/10.1186/s12885-015-1802-z] [PMID: 26497576]
[47]
Brugnoli, F.; Grassilli, S.; Lanuti, P.; Marchisio, M.; Al-Qassab, Y.; Vezzali, F.; Capitani, S.; Bertagnolo, V. Up-modulation of PLC-β2 reduces the number and malignancy of triple-negative breast tumor cells with a CD133+/EpCAM+ phenotype: A promising target for preventing progression of TNBC. BMC Cancer, 2017, 17(1), 617.
[http://dx.doi.org/10.1186/s12885-017-3592-y] [PMID: 28870198]
[48]
Bertagnolo, V.; Grassilli, S.; Volinia, S.; Al-Qassab, Y.; Brugnoli, F.; Vezzali, F.; Lambertini, E.; Palomba, M.; Piubello, Q.; Orvieto, E.; Natali, C.; Piva, R.; Croce, C.M.; Capitani, S. Ectopic expression of PLC-β2 in non-invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR-146a. Mol. Carcinog., 2019, 58(5), 708-721.
[http://dx.doi.org/10.1002/mc.22964] [PMID: 30582225]
[49]
Park, M.S.; Lee, Y.E.; Kim, H.R.; Shin, J.H.; Cho, H.W.; Lee, J.H.; Shin, M.G.; Phospholipase, C. Phospholipase C beta 2 protein overexpression is a favorable prognostic indicator in newly diagnosed normal karyotype acute myeloid leukemia. Ann. Lab. Med., 2021, 41(4), 409-413.
[http://dx.doi.org/10.3343/alm.2021.41.4.409] [PMID: 33536360]
[50]
Bach, T.L.; Chen, Q.M.; Kerr, W.T.; Wang, Y.; Lian, L.; Choi, J.K.; Wu, D.; Kazanietz, M.G.; Koretzky, G.A.; Zigmond, S.; Abrams, C.S. Phospholipase cbeta is critical for T cell chemotaxis. J. Immunol., 2007, 179(4), 2223-2227.
[http://dx.doi.org/10.4049/jimmunol.179.4.2223] [PMID: 17675482]
[51]
Grinberg, S.; Hasko, G.; Wu, D.; Leibovich, S.J. Suppression of PLCbeta2 by endotoxin plays a role in the adenosine A(2A) receptor-mediated switch of macrophages from an inflammatory to an angiogenic phenotype. Am. J. Pathol., 2009, 175(6), 2439-2453.
[http://dx.doi.org/10.2353/ajpath.2009.090290] [PMID: 19850892]
[52]
Kawakami, T.; Xiao, W. Phospholipase C-β in immune cells. Adv. Biol. Regul., 2013, 53(3), 249-257.
[http://dx.doi.org/10.1016/j.jbior.2013.08.001] [PMID: 23981313]
[53]
Uttamani, J.R.; Naqvi, A.R.; Estepa, A.M.V.; Kulkarni, V.; Brambila, M.F.; Martínez, G.; Chapa, G.; Wu, C.D.; Li, W.; Rivas-Tumanyan, S. Downregulation of miRNA-26 in chronic periodontitis interferes with innate immune responses and cell migration by targeting phospholipase C beta 1 (PLCB1). J. Clin. Periodontol., 2022, 50(1), 102–113.
[http://dx.doi.org/10.1111/jcpe.13715] [PMID: 36054706]
[54]
Owusu Obeng, E.; Rusciano, I.; Marvi, M.V.; Fazio, A.; Ratti, S.; Follo, M.Y.; Xian, J.; Manzoli, L.; Billi, A.M.; Mongiorgi, S.; Ramazzotti, G.; Cocco, L. Phosphoinositide-dependent signaling in cancer: A focus on phospholipase C isozymes. Int. J. Mol. Sci., 2020, 21(7), 2581.
[http://dx.doi.org/10.3390/ijms21072581] [PMID: 32276377]
[55]
Zhu, L.; Jones, C.; Zhang, G. The role of phospholipase C signaling in macrophage-mediated inflammatory response. J. Immunol. Res., 2018, 2018, 1-9.
[http://dx.doi.org/10.1155/2018/5201759] [PMID: 30057916]
[56]
Wang, L.; Zhou, Y.; Chen, Z.; Sun, L.; Wu, J.; Li, H.; Liu, F.; Wang, F.; Yang, C.; Yang, J.; Leng, Q.; Zhang, Q.; Xu, A.; Shen, L.; Sun, J.; Wu, D.; Fang, C.; Lu, H.; Yan, D.; Ge, B. PLCβ2 negatively regulates the inflammatory response to virus infection by inhibiting phosphoinositide-mediated activation of TAK1. Nat. Commun., 2019, 10(1), 746.
[http://dx.doi.org/10.1038/s41467-019-08524-3] [PMID: 30765691]
[57]
Liskamp, R.M.J.; Rijkers, D.T.S.; Kruijtzer, J.A.W.; Kemmink, J. Peptides and proteins as a continuing exciting source of inspiration for peptidomimetics. ChemBioChem, 2011, 12(11), 1626-1653.
[http://dx.doi.org/10.1002/cbic.201000717] [PMID: 21751324]
[58]
Fosgerau, K.; Hoffmann, T. Peptide therapeutics: Current status and future directions. Drug Discov. Today, 2015, 20(1), 122-128.
[http://dx.doi.org/10.1016/j.drudis.2014.10.003] [PMID: 25450771]
[59]
Kumar, A.; Kothari, J.; Lokhande, K.B.; Seethamma, T.N.; Venkateswara Swamy, K.; Sharma, N.K. Novel antiproliferative tripeptides inhibit AP-1 transcriptional complex. Int. J. Pept. Res. Ther., 2021, 27(4), 2163-2182.
[http://dx.doi.org/10.1007/s10989-021-10244-6]
[60]
Sharma, N.K.; Ajay, K.; Asawari, W. Design of vertical tube electrophoretic system and method to fractionate small molecular weight compounds using polyacrylamide gel matrix. Patent 201921000760, 2018.
[61]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19(14), 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B]
[62]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2009, 31(2), 455-461.
[http://dx.doi.org/10.1002/jcc.21334] [PMID: 19499576]
[63]
DSV3. Discovery Studio Visualizer v3.0. Accelrys software inc; , 2010.
[64]
Release, S. 2019-4: Desmond Molecular Dynamics System; D. E. Shaw Research: New York, 2019.
[65]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7(1), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]

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