Evaluation of glycyl-arginine and lysyl-aspartic acid dipeptides for their antimicrobial, antibiofilm, and anticancer potentials.

Handan Sevim Akan, Gülcan Şahal, Tuğçe Deniz Karaca, Özer Aylin Gürpınar, Meltem Maraş, Alev Doğan
Author Information
  1. Handan Sevim Akan: Department Biology, Faculty of Science, Hacettepe University, Beytepe, Cankaya, 06800, Ankara, Turkey. sevimh@hacettepe.edu.tr. ORCID
  2. Gülcan Şahal: Department Biology, Faculty of Science, Hacettepe University, Beytepe, Cankaya, 06800, Ankara, Turkey. ORCID
  3. Tuğçe Deniz Karaca: Department of Medical Services and Techniques, Gazi University Health Service Vocational School, Ankara, Turkey. ORCID
  4. Özer Aylin Gürpınar: Department Biology, Faculty of Science, Hacettepe University, Beytepe, Cankaya, 06800, Ankara, Turkey. ORCID
  5. Meltem Maraş: Department of Mathematics and Science Education, Faculty of Education Ereğli, Bülent Ecevit University, Zonguldak, Turkey. ORCID
  6. Alev Doğan: Department of Science Education, Faculty of Gazi Education, Gazi University, Teknikokullar, Ankara, Turkey. ORCID

Abstract

Antibacterial resistance and cancer are worldwide challenges and have been defined as major threats by international health organizations. Peptides are produced naturally by all organisms and have a variety of immunomodulatory, physiological, and wound-healing properties. They can also provide protection against microorganisms and tumor cells. Therefore, we aimed to determine the antimicrobial, antibiofilm, and anticancer potentials of glycyl-arginine and Lysyl-Aspartic acid dipeptides. The Broth Dilution and Crystal Violet Binding assays assessed the antimicrobial tests and biofilm inhibitory effects. The MTT assay was used to measure the cytotoxic effects of dipeptides on HeLa cell viability. According to our results, Candida tropicalis T26 and Proteus mirabilis U15 strains were determined as more resistant to Staphylococcus epidermidis W17 against glycyl-arginine and Lysyl-Aspartic acid dipeptides with MICs higher than 2 mM (1 mg/mL). Sub-MICs of glycyl-arginine caused inhibitions against biofilm formation of all the tested clinical isolates, with the highest inhibition observed against S. epidermidisW17. Lysyl-Aspartic acid exhibited zero to no effect against biofilm formation of P. mirabilisU15, and S. epidermidisW17, whereas it exhibited 52% inhibition of biofilm formation of C. tropicalisT26. Cell viability results revealed that HeLa cell viability decreases with increasing concentration of both dipeptides. Also, parallel to antimicrobial tests, glycyl-arginine has a greater cytotoxic effect compared to Lysyl-Aspartic acid. The findings from this study will contribute to the advancement of novel strategies involving dipeptide-based synthesizable molecules and drug development studies. However, it is essential to note that there are still challenges, including the need for extensive experimental and clinical trials.

Keywords

References

  1. Agarwal S, Sharma G, Dang S, Gupta S, Gabrani R (2016) Antimicrobial peptides as anti-infectives against Staphylococcus epidermidis. Med Princ Pract 25(4):301–308. https://doi.org/10.1159/000443479 [DOI: 10.1159/000443479]
  2. Alsalhi A, Ayon NJ, Coulibaly F, Alshamrani M, Al-Nafisah A, Youan B-BC (2021) Enhancing etoposide aqueous solubility and anticancer activity with L-Arginine. Assay Drug Dev Technol 19(8):508–525. https://doi.org/10.1089/adt.2021.085 [DOI: 10.1089/adt.2021.085]
  3. Attah SI, Okoro UC, Singh SP, Eze CC, Ibeji CU, Ezugwu JA, Okenyeka OU, Ekoh O, Ugwu DI, Eze FU (2022) Pro-Gly based dipeptide containing sulphonamide functionality, their antidiabetic, antioxidant, and anti-inflammatory activities. Synthesis, characterization and computational studies. J Mol Struct 1264:133280. https://doi.org/10.1016/j.molstruc.2022.133280 [DOI: 10.1016/j.molstruc.2022.133280]
  4. Baxter AA, Lay FT, Poon IK, Kvansakul M, Hulett MD (2017) Tumor cell membrane-targeting cationic antimicrobial peptides: novel insights into mechanisms of action and therapeutic prospects. Cell Mol Life Sci 74(20):3809–3825. https://doi.org/10.1007/s00018-017-2604-z [DOI: 10.1007/s00018-017-2604-z]
  5. Bijle MNA, Ekambaram M, Lo E, Yiu CKY (2019) The combined antimicrobial effect of arginine and fluoride toothpaste. Sci Rep 9(1):1–10. https://doi.org/10.1038/s41598-019-44612-6 [DOI: 10.1038/s41598-019-44612-6]
  6. Bizerra FC, Nakamura CV, De Poersch C, Estivalet Svidzinski TI, Borsato Quesada RM, Goldenberg S, Krieger MA, Yamada-Ogatta SF (2008) Characteristics of biofilm formation by Candida tropicalis and antifungal resistance. FEMS Yeast Res 8(3):442–450. https://doi.org/10.1111/j.1567-1364.2007.00347.x [DOI: 10.1111/j.1567-1364.2007.00347.x]
  7. Brogden NK, Brogden KA (2011) Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals? Int J Antimicrob Agents 38(3):217–225. https://doi.org/10.1016/j.ijantimicag.2011.05.004 [DOI: 10.1016/j.ijantimicag.2011.05.004]
  8. Çakmak G, Akay C, Donmez MB, Mumcu E, Akan HS, Sasany R, Abou-Ayash S, Yilmaz B (2022) Effect of potassium aluminum sulfate application on the viability of fibroblasts on a cad-cam feldspathic ceramic before and after thermocycling. Materials 15(12):4232 [DOI: 10.3390/ma15124232]
  9. Can HK, Sevim H, Şahin Ö, Gürpınar ÖA (2021) Experimental routes of cytotoxicity studies of nanocomposites based on the organo-bentonite clay and anhydride containing co-and terpolymers. Polym Bull. https://doi.org/10.1007/s00289-021-03776-w [DOI: 10.1007/s00289-021-03776-w]
  10. Das MC, Samaddar S, Jawed JJ, Ghosh C, Acharjee S, Sandhu P, Das A, Daware AV, De UC, Majumdar S (2022) Vitexin alters Staphylococcus aureus surface hydrophobicity to obstruct biofilm formation. Microbiol Res 263:127126. https://doi.org/10.1016/j.micres.2022.127126 [DOI: 10.1016/j.micres.2022.127126]
  11. Day T, Greenfield S (2004) Bioactivity of a peptide derived from acetylcholinesterase in hippocampal organotypic cultures. Exp Brain Res 155:500–508. https://doi.org/10.1007/s00221-003-1757-1 [DOI: 10.1007/s00221-003-1757-1]
  12. Ezugwu JA, Okoro UC, Ezeokonkwo MA, Bhimapaka C, Okafor SN, Ugwu DI, Ugwuja DI (2020a) Synthesis and biological evaluation of Val–Val dipeptide–sulfonamide conjugates. Arch Pharm 353(7):2000074. https://doi.org/10.1002/ardp.202000074 [DOI: 10.1002/ardp.202000074]
  13. Ezugwu JA, Okoro UC, Ezeokonkwo MA, Bhimapaka CR, Okafor SN, Ugwu DI, Ekoh OC, Attah SI (2020b) Novel Leu-Val based dipeptide as antimicrobial and antimalarial agents: Synthesis and molecular docking. Front Chem 8:583926. https://doi.org/10.3389/fchem.2020.583926 [DOI: 10.3389/fchem.2020.583926]
  14. Fait ME, Grillo PD, Garrote GL, Prieto ED, Vázquez RF, Saparrat MC, Morcelle SR (2023) Biocidal and antibiofilm activities of arginine-based surfactants against Candida isolates. Amino Acids. https://doi.org/10.1007/s00726-023-03296-z [DOI: 10.1007/s00726-023-03296-z]
  15. Gabernet G, Müller AT, Hiss JA, Schneider G (2016) Membranolytic anticancer peptides. Medchemcomm 7(12):2232–2245. https://doi.org/10.1039/C6MD00376A [DOI: 10.1039/C6MD00376A]
  16. Gao L-J, De Jonghe S, Daelemans D, Herdewijn P (2016) l-Aspartic and l-glutamic acid ester-based ProTides of anticancer nucleosides: synthesis and antitumoral evaluation. Bioorg Med Chem Lett 26(9):2142–2146. https://doi.org/10.1016/j.bmcl.2016.03.076 [DOI: 10.1016/j.bmcl.2016.03.076]
  17. Gaspar D, Veiga AS, Castanho MA (2013) From antimicrobial to anticancer peptides. A review. Front Microbiol 4:294. https://doi.org/10.3389/fmicb.2013.00294 [DOI: 10.3389/fmicb.2013.00294]
  18. Ghosh C, Bhowmik J, Ghosh R, Das MC, Sandhu P, Kumari M, Acharjee S, Daware AV, Akhter Y, Banerjee B (2020) The anti-biofilm potential of triterpenoids isolated from Sarcochlamys pulcherrima (Roxb.) Gaud. Microb Pathog 139:103901. https://doi.org/10.1016/j.micpath.2019.103901 [DOI: 10.1016/j.micpath.2019.103901]
  19. Hadianamrei R, Tomeh MA, Brown S, Wang J, Zhao X (2022) Rationally designed short cationic α-helical peptides with selective anticancer activity. J Colloid Interface Sci 607:488–501. https://doi.org/10.1016/j.jcis.2021.08.200 [DOI: 10.1016/j.jcis.2021.08.200]
  20. Hadley EB, Hancock REW (2010) Strategies for the discovery and advancement of novel cationic antimicrobial peptides. Curr Top Med Chem 10(18):1872–1881. https://doi.org/10.2174/156802610793176648 [DOI: 10.2174/156802610793176648]
  21. Hajipour H, Ghorbani M, Kahroba H, Mahmoodzadeh F, Emameh RZ, Taheri RA (2019) Arginyl-glycyl-aspartic acid (RGD) containing nanostructured lipid carrier co-loaded with doxorubicin and sildenafil citrate enhanced anti-cancer effects and overcomes drug resistance. Process Biochem 84:172–179. https://doi.org/10.1016/j.procbio.2019.06.013 [DOI: 10.1016/j.procbio.2019.06.013]
  22. Hanahan D (2022) Hallmarks of cancer: new dimensions. Cancer Discov 12(1):31–46. https://doi.org/10.1158/2159-8290.CD-21-1059 [DOI: 10.1158/2159-8290.CD-21-1059]
  23. Huang W, Lu L, Shao X, Tang C, Zhao X (2010) Anti-melanoma activity of hybrid peptide P18 and its mechanism of action. Biotech Lett 32:463–469. https://doi.org/10.1007/s10529-009-0175-2 [DOI: 10.1007/s10529-009-0175-2]
  24. Iwasaki T, Ishibashi J, Tanaka H, Sato M, Asaoka A, Taylor D, Yamakawa M (2009) Selective cancer cell cytotoxicity of enantiomeric 9-mer peptides derived from beetle defensins depends on negatively charged phosphatidylserine on the cell surface. Peptides 30(4):660–668. https://doi.org/10.1016/j.peptides.2008.12.019 [DOI: 10.1016/j.peptides.2008.12.019]
  25. Kapil S, Sharma V (2021) d-Amino acids in antimicrobial peptides: a potential approach to treat and combat antimicrobial resistance. Can J Microbiol 67(2):119–137. https://doi.org/10.1139/cjm-2020-0142 [DOI: 10.1139/cjm-2020-0142]
  26. Karaca TD, Balci H, Aysan A (2023) Evaluation and comparison of the antimicrobial and cytotoxic activities of some amino acid methyl esters. Hacettepe J Biol Chem 51(2):1–8. https://doi.org/10.15671/hjbc.1183477 [DOI: 10.15671/hjbc.1183477]
  27. Kim MK, Kang HK, Ko SJ, Hong MJ, Bang JK, Seo CH, Park Y (2018) Mechanisms driving the antibacterial and antibiofilm properties of Hp1404 and its analogue peptides against multidrug-resistant Pseudomonas aeruginosa. Sci Rep 8(1):1763. https://doi.org/10.1038/s41598-018-19434-7 [DOI: 10.1038/s41598-018-19434-7]
  28. Koran K, Çalışkan E, Öztürk DA, Çapan İ, Tekin S, Sandal S, Görgülü AO (2023) The first peptide derivatives of dioxybiphenyl-bridged spiro cyclotriphosphazenes: in vitro cytotoxicity activities and DNA damage studies. Bioorg Chem 132:106338. https://doi.org/10.1016/j.bioorg.2022.106338 [DOI: 10.1016/j.bioorg.2022.106338]
  29. Kurrikoff K, Aphkhazava D, Langel Ü (2019) The future of peptides in cancer treatment. Curr Opin Pharmacol 47:27–32. https://doi.org/10.1016/j.coph.2019.01.008 [DOI: 10.1016/j.coph.2019.01.008]
  30. Lath A, Santal AR, Kaur N, Kumari P, Singh NP (2023) Anti-cancer peptides: their current trends in the development of peptide-based therapy and anti-tumor drugs. Biotechnol Genet Eng Rev 39(1):45–84. https://doi.org/10.1080/02648725.2022.2082157 [DOI: 10.1080/02648725.2022.2082157]
  31. Lim YY, Zaidi AMA, Haque M, Miskon A (2023a) Relationship between tumorigenesis, metastasis, immune evasion, and chemoresistance in osteosarcoma therapy. J Appl Pharm Sci. https://doi.org/10.7324/JAPS.2023.149907 [DOI: 10.7324/JAPS.2023.149907]
  32. Lim YY, Zaidi AMA, Miskon A (2023b) Combining copper and zinc into a biosensor for anti-chemoresistance and achieving osteosarcoma therapeutic efficacy. Molecules 28(7):2920. https://doi.org/10.3390/molecules28072920 [DOI: 10.3390/molecules28072920]
  33. Lin Q, Fang D, Hou X, Le Y, Fang J, Wen F, Gong W, Chen K, Wang JM, Su SB (2011) HCV peptide (C5A), an amphipathic α-helical peptide of hepatitis virus C, is an activator of N-formyl peptide receptor in human phagocytes. J Immunol 186(4):2087–2094. https://doi.org/10.4049/jimmunol.1002340 [DOI: 10.4049/jimmunol.1002340]
  34. Mba IE, Nweze EI (2022) Focus: antimicrobial resistance: antimicrobial peptides therapy: an emerging alternative for treating drug-resistant bacteria. Yale J Biol Med 95(4):445 [PMID: 36568838]
  35. Mercer DK, Torres MD, Duay SS, Lovie E, Simpson L, von Köckritz-Blickwede M, De la Fuente-Nunez C, O’Neil DA, Angeles-Boza AM (2020) Antimicrobial susceptibility testing of antimicrobial peptides to better predict efficacy. Front Cell Infect Microbiol. https://doi.org/10.3389/fcimb.2020.00326 [DOI: 10.3389/fcimb.2020.00326]
  36. Minami M, Ando T, Hashikawa S-n, Torii K, Hasegawa T, Israel DA, Ina K, Kusugami K, Goto H, Ohta M (2004) Effect of glycine on Helicobacter pylori in vitro. Antimicrob Agents Chemother 48(10):3782–3788. https://doi.org/10.1128/AAC.48.10.3782-3788.2004 [DOI: 10.1128/AAC.48.10.3782-3788.2004]
  37. Mwangi J, Hao X, Lai R, Zhang Z-Y (2019) Antimicrobial peptides: new hope in the war against multidrug resistance. Zoo Res 40(6):488. https://doi.org/10.24272/j.issn.2095-8137.2019.062 [DOI: 10.24272/j.issn.2095-8137.2019.062]
  38. Negri M, Silva S, Breda D, Henriques M, Azeredo J, Oliveira R (2012) Candida tropicalis biofilms: effect on urinary epithelial cells. Microb Pathog 53(2):95–99. https://doi.org/10.1016/j.micpath.2012.05.006 [DOI: 10.1016/j.micpath.2012.05.006]
  39. Nikfar Z, Shariatinia Z (2020) Tripeptide arginyl-glycyl-aspartic acid (RGD) for delivery of Cyclophosphamide anticancer drug: a computational approach. Int J Nano Dimens 11(4):312–336
  40. Nitta A, Nishioka H, Fukumitsu H, Furukawa Y, Sugiura H, Shen L, Furukawa S (2004) Hydrophobic dipeptide Leu-Ile protects against neuronal death by inducing brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor synthesis. J Neurosci Res 78(2):250–258. https://doi.org/10.1002/jnr.20258 [DOI: 10.1002/jnr.20258]
  41. Raheem N, Straus SK (2019) Mechanisms of action for antimicrobial peptides with antibacterial and antibiofilm functions. Front Microbiol 10:2866 [DOI: 10.3389/fmicb.2019.02866]
  42. Rahman R, Fonseka AD, Sua SC, Ahmad M, Rajendran R, Ambu S, Davamani F, Khoo ASB, Chitra E (2021) Inhibition of breast cancer xenografts in a mouse model and the induction of apoptosis in multiple breast cancer cell lines by lactoferricin B peptide. J Cell Mol Med 25(15):7181–7189. https://doi.org/10.1111/jcmm.16748 [DOI: 10.1111/jcmm.16748]
  43. Ranjbar HH, Abari AH, Ghasemi SM, Ghorbani N (2022) Antioxidant and anticancer effects of Epsilon-Poly-L-lysine produced by two novel strains of Paenibacillus polymyxa HS6 and Stenotrophomonas maltophilia YS8. Biotech Bioprocess Eng 27(4):586–595. https://doi.org/10.1007/s12257-022-0065-1 [DOI: 10.1007/s12257-022-0065-1]
  44. Ryu M, Park J, Yeom J-H, Joo M, Lee K (2021) Rediscovery of antimicrobial peptides as therapeutic agents. J Microbiol 59:113–123. https://doi.org/10.1007/s12275-021-0649-z [DOI: 10.1007/s12275-021-0649-z]
  45. Sahal G, Bilkay IS (2014) Multi drug resistance in strong biofilm forming clinical isolates of Staphylococcus epidermidis. Braz J Microbiol 45:539–544. https://doi.org/10.1590/S1517-83822014005000042 [DOI: 10.1590/S1517-83822014005000042]
  46. Sahal G, Bilkay IS (2015) Multidrug resistance by biofilm-forming clinical strains of. Asian Biomed 9(4):535–541. https://doi.org/10.5372/1905-7415.0904.424 [DOI: 10.5372/1905-7415.0904.424]
  47. Sahal G, Bilkay IS (2018) Distribution of clinical isolates of Candida spp. and antifungal susceptibility of high biofilm-forming Candida isolates. Rev Soc Bras Med Trop 51:644–650. https://doi.org/10.1590/0037-8682-0136-2018 [DOI: 10.1590/0037-8682-0136-2018]
  48. Schaffer JN, Pearson MM (2017) Proteus mirabilis and urinary tract infections. Urinary Tract Infect. https://doi.org/10.1590/0037-8682-0136-2018383-433 [DOI: 10.1590/0037-8682-0136-2018383-433]
  49. Severn MM, Horswill AR (2023) Staphylococcus epidermidis and its dual lifestyle in skin health and infection. Nat Rev Microbiol 21(2):97–111. https://doi.org/10.1038/s41579-022-00780-3 [DOI: 10.1038/s41579-022-00780-3]
  50. Siegel RL, Miller KD, Wagle NS, Jemal A (2023) Cancer statistics, 2023. CA Cancer J Clin 73(1):17–48. https://doi.org/10.3322/caac.21763 [DOI: 10.3322/caac.21763]
  51. Song SJ, Choi JS (2022) Enzyme-responsive amphiphilic peptide nanoparticles for biocompatible and efficient drug delivery. Pharmaceutics 14(1):143. https://doi.org/10.3390/pharmaceutics14010143 [DOI: 10.3390/pharmaceutics14010143]
  52. Stefanowicz-Hajduk J, Ochocka JR (2020) Real-time cell analysis system in cytotoxicity applications: usefulness and comparison with tetrazolium salt assays. Toxicol Rep 7:335–344. https://doi.org/10.1016/j.toxrep.2020.02.002 [DOI: 10.1016/j.toxrep.2020.02.002]
  53. Švedienė J, Novickij V, Žalnėravičius R, Raudonienė V, Markovskaja S, Novickij J, Paškevičius A (2021) Antimicrobial activity of L-lysine and poly-L-lysine with pulsed electric fields. Appl Sci 11(6):2708. https://doi.org/10.3390/app11062708 [DOI: 10.3390/app11062708]
  54. Szende B, Szökán G, Tyihá E, Pál K, Gáborjányi R, Almás M, Khlafulla A (2002) Antitumor effect of lysine-isopeptides. Cancer Cell Int 2:1–7 [DOI: 10.1186/1475-2867-2-4]
  55. Wu H, Moser C, Wang H-Z, Høiby N, Song Z-J (2015) Strategies for combating bacterial biofilm infections. Int J Oral Sci 7(1):1–7. https://doi.org/10.1038/ijos.2014.65 [DOI: 10.1038/ijos.2014.65]
  56. Xie M, Liu D, Yang Y (2020) Anti-cancer peptides: classification, mechanism of action, reconstruction and modification. Open Biol 10(7):200004. https://doi.org/10.1098/rsob.200004 [DOI: 10.1098/rsob.200004]
  57. Yamaguchi Y, Yamamoto K, Sato Y, Inoue S, Morinaga T, Hirano E (2016) Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation. Biomed Res 37(2):153–159. https://doi.org/10.2220/biomedres.37.153 [DOI: 10.2220/biomedres.37.153]
  58. Yousefi MH, Afkhami H, Akbari A, Honari H (2023) Expression, purification, characterization, and cytotoxic evaluation of the ML1-STxB fusion protein. Arch Microbiol 205(6):220. https://doi.org/10.1007/s00203-023-03563-3 [DOI: 10.1007/s00203-023-03563-3]
  59. Zhang Q-Y, Yan Z-B, Meng Y-M, Hong X-Y, Shao G, Ma J-J, Cheng X-R, Liu J, Kang J, Fu C-Y (2021) Antimicrobial peptides: mechanism of action, activity and clinical potential. Mil Med Res 8:1–25. https://doi.org/10.1186/s40779-021-00343-2 [DOI: 10.1186/s40779-021-00343-2]
  60. Zhang H, Wu J, Wang J, Xiao S, Zhao L, Yan R, Wu X, Wang Z, Fan L, Jin Y (2022) Novel isoindolinone-based analogs of the natural cyclic peptide fenestin a: synthesis and antitumor activity. ACS Med Chem Lett 13(7):1118–1124. https://doi.org/10.1021/acsmedchemlett.2c00149 [DOI: 10.1021/acsmedchemlett.2c00149]

MeSH Term

Humans
Anti-Bacterial Agents
Anti-Infective Agents
Aspartic Acid
Biofilms
Dipeptides
HeLa Cells
Microbial Sensitivity Tests
Antineoplastic Agents

Chemicals

Anti-Bacterial Agents
Anti-Infective Agents
Aspartic Acid
Dipeptides
Antineoplastic Agents

Word Cloud

Created with Highcharts 10.0.0aciddipeptidesantimicrobialGlycyl-ArginineLysyl-AsparticbiofilmviabilityformationeffectchallengesantibiofilmanticancerpotentialstestseffectscytotoxicHeLacellresultsclinicalinhibitionSepidermidisW17exhibitedAntibacterialresistancecancerworldwidedefinedmajorthreatsinternationalhealthorganizationsPeptidesproducednaturallyorganismsvarietyimmunomodulatoryphysiologicalwound-healingpropertiescanalsoprovideprotectionmicroorganismstumorcellsThereforeaimeddetermineBrothDilutionCrystalVioletBindingassaysassessedinhibitoryMTTassayusedmeasureAccordingCandida tropicalisT26ProteusmirabilisU15strainsdeterminedresistantStaphylococcus epidermidisW17MICshigher2 mM1 mg/mLSub-MICscausedinhibitionstestedisolateshighestobservedzeroPmirabilisU15whereas52%CtropicalisT26CellrevealeddecreasesincreasingconcentrationAlsoparallelgreatercomparedfindingsstudywillcontributeadvancementnovelstrategiesinvolvingdipeptide-basedsynthesizablemoleculesdrugdevelopmentstudiesHoweveressentialnotestillincludingneedextensiveexperimentaltrialsEvaluationglycyl-argininelysyl-asparticAntibiofilmAnticanceractivityAntimicrobialsCytotoxicityGlycyl-arginineLysyl-aspartic

Similar Articles

Cited By (1)