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Stability assessment of a new antithrombotic small peptide, Arg-Gly-Asp-Trp-Arg (RGDWR), and its derivative

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Abstract

Objective

To assess the stabilities of Arg-Gly-Asp-Trp-Arg (RGDWR, designated as RWR), a new patented antithrombotic small peptide, and its derivative with ω-aminocaprylic acid on its N-terminus (ωRWR).

Results

RWR in rat plasma was decreased by between 32 and 48% after 4 h incubation on ice, indicating its instability in plasma. In contrast, ωRWR in plasma remained at 96–107%. Concentration changes were within 6.2% for ωRWR after storage in various conditions. ωRWR is therefore stable in rat plasma, as well as under different storage methods. Furthermore, ω-aminocaprylic acid added onto the RWR peptide did not affect its antiplatelet aggregation activity.

Conclusions

A novel small peptide, ωRWR, has been developed with a good stability for possible antithrombotic use.

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References

  • Amin M, Mansourian M, Koning GA, Badiee A, Jaafari MR, ten Hagen TL (2015) Development of a novel cyclic RGD peptide for multiple targeting approaches of liposomes to tumor region. J Control Rel 220:308–315

    Article  CAS  Google Scholar 

  • Assumpcao TC, Ribeiro JM, Francischetti IM (2012) Disintegrins from hematophagous sources. Toxins 4:296–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blue R, Kowalska MA, Hirsch J, Murcia M, Janczak CA, Harrington A, Jirouskova M, Li J, Fuentes R, Thornton MA, Filizola M, Poncz M, Coller BS (2009) Structural and therapeutic insights from the species specificity and in vivo antithrombotic activity of a novel alphaIIb-specific alphaIIbbeta3 antagonist. Blood 114:195–201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bol’shakov OI, Akala EO (2014) MS-monitored conjugation of poly(ethylene glycol) monomethacrylate to RGD peptides. J Appl Polym Sci Symp 131:40385

    PubMed  PubMed Central  Google Scholar 

  • Chen H, Niu G, Wu H, Chen X (2016) Clinical application of radiolabeled RGD peptides for PET imaging of integrin alphavbeta3. Theranostics 6:78–92

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cho J, Mosher DF (2006) Enhancement of thrombogenesis by plasma fibronectin cross-linked to fibrin and assembled in platelet thrombi. Blood 107:3555–3563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cui W, Di X (2015) Clinical application of new antithrombotic drugs. Chin J Cardio Med 20:328–333

    Google Scholar 

  • Durkan K, Jiang Z, Rold TL, Sieckman GL, Hoffman TJ, Bandari RP, Szczodroski AF, Liu L, Miao Y, Reynolds TS, Smith CJ (2014) A heterodimeric [RGD-Glu-[(64)Cu-NO2A]-6-Ahx-RM2] alphavbeta3/GRPr-targeting antagonist radiotracer for PET imaging of prostate tumors. Nucl Med Biol 41:133–139

    Article  CAS  PubMed  Google Scholar 

  • Feng C, Li X, Dong C, Zhang X, Zhang X, Gao Y (2015) RGD-modified liposomes enhance efficiency of aclacinomycin A delivery: evaluation of their effect in lung cancer. Drug Des Devel Ther 9:4613–4620

    PubMed  PubMed Central  Google Scholar 

  • Hagemeyer CE, Peter K (2010) Targeting the platelet integrin GPIIb/IIIa. Curr Pharm Des 16:4119–4133

    Article  CAS  PubMed  Google Scholar 

  • Hoekman JD, Srivastava P, Ho RJ (2014) Aerosol-stable peptide-coated liposome nanoparticles: a proof-of-concept study with opioid fentanyl in enhancing analgesic effects and reducing plasma drug exposure. J Pharm Sci 103:2231–2239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lamande-Langle S, Collet C, Hensienne R, Vala C, Chretien F, Chapleur Y, Mohamadi A, Lacolley P, Regnault V (2014) ‘Click’ glycosylation of peptides through cysteine propargylation and CuAAC. Bioorg Med Chem 22:6672–6683

    Article  CAS  PubMed  Google Scholar 

  • Lei Y, Wang J, Xie C, Wagner E, Lu W, Li Y, Wei X, Dong J, Liu M (2013) Glutathione-sensitive RGD-poly(ethylene glycol)-SS-polyethylenimine for intracranial glioblastoma targeted gene delivery. J Gene Med 15:291–305

    CAS  PubMed  Google Scholar 

  • Maschauer S, Haubner R, Kuwert T, Prante O (2014) (18)F-glyco-RGD peptides for PET imaging of integrin expression: efficient radiosynthesis by click chemistry and modulation of biodistribution by glycosylation. Mol Pharm 11:505–515

    Article  CAS  PubMed  Google Scholar 

  • Meyer dos Santos S, Kuczka K, Picard-Willems B, Nelson K, Klinkhardt U, Harder S (2015) The integrin antagonist, cilengitide, is a weak inhibitor of alphaIIbbeta3 mediated platelet activation and inhibits platelet adhesion under flow. Platelets 26:59–66

    Article  CAS  PubMed  Google Scholar 

  • O’Connor A, Marsat JN, Mitrugno A, Flahive T, Moran N, Brayden D, Devocelle M (2014) Poly(Ethylene glycol)-based backbones with high peptide loading capacities. Molecules 19:17559–17577

    Article  PubMed  Google Scholar 

  • Rutherfurd KJ, Gill HS (2000) Peptides affecting coagulation. Br J Nutr 84(Suppl 1):S99–102

    CAS  PubMed  Google Scholar 

  • Ungerer M, Munch G (2013) Novel antiplatelet drugs in clinical development. Thromb Haemost 110:868–875

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Zhao Y, Sun R, Kong W, Wang B, Yang G, Li Y (2015) Discovery of novel antagonists of glycoprotein IIb/IIIa-mediated platelet aggregation through virtual screening. Bioorg Med Chem Lett 25:1249–1253

    Article  CAS  PubMed  Google Scholar 

  • Yang T, Niu B, Cheng NL (2009) Replacement of RGD motif with RGDNM attenuates echistatin’s anti-platelet aggregation effect, but enhances its inhibition on angiogenesis. Chin J Biochem Mol Biol 25:834–838

    CAS  Google Scholar 

  • Yang L-J, Niu B, Zhang D, Yang T (2015) Substitution of the Echistatin amino acid motif RGDD with KGDW enhances inhibition of platelet aggregation and thrombogenesis. Int J Pept Res Ther 21:451–458

    Article  CAS  Google Scholar 

  • Zhang J, Mujeeb A, Du Y, Lin J, Ge Z (2015) Probing cell-matrix interactions in RGD-decorated macroporous poly (ethylene glycol) hydrogels for 3D chondrocyte culture. Biomed Mater 10:035016

    Article  PubMed  Google Scholar 

  • Zhao H, Yang T, Yang L (2013) The impact of receptor action of RWR by integrin αIIbβ3 on platelet surface on thrombosis. Chin J Biol 26:1126–1129

    CAS  Google Scholar 

  • Zhen Z, Tang W, Chen H, Lin X, Todd T, Wang G, Cowger T, Chen X, Xie J (2013) RGD-modified apoferritin nanoparticles for efficient drug delivery to tumors. ACS Nano 7:4830–4837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng H, Zhao H, Wang SH (2015) Experimental study of toxicology of antithrombotic small peptides RWR. Chin J Biochem Pharm 35:6–10

    CAS  Google Scholar 

Download references

Acknowledgements

We appreciate Prof. Gongqin Sun from the University of Rhode Island for carefully proofreading the manuscript during revision. This study was supported by the National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Twelfth Five-year Plan Period (2012ZX09103301-010), the Youth Fund of National Natural Science Fund (81101895), the Research Project Supported by Shanxi Scholarship Council of China (2016-050), and the Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Province (2014-179).

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Author notes

  1. Lijun Yang and Litao Zhang have been contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Lijun Yang, Litao Zhang, Lihong Yan, Haifeng Zheng, Peifen Lu, Junjun Chen, Jie Dai & Tao Yang

  2. Department of Orthopedics, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Haibiao Sun

  3. Department of Psychiatry, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, China

    Yong Xu

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  1. Lijun Yang
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  2. Litao Zhang
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  3. Lihong Yan
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  4. Haifeng Zheng
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  5. Peifen Lu
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  6. Junjun Chen
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  7. Jie Dai
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  8. Haibiao Sun
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  9. Yong Xu
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  10. Tao Yang
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Corresponding author

Correspondence to Tao Yang.

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All authors declare that they have no conflict of interests.

Ethical approval

All animal procedures were approved by the Animal Care and Scientific Committee of Shanxi Medical University.

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Yang, L., Zhang, L., Yan, L. et al. Stability assessment of a new antithrombotic small peptide, Arg-Gly-Asp-Trp-Arg (RGDWR), and its derivative. Biotechnol Lett 39, 1183–1190 (2017). https://doi.org/10.1007/s10529-017-2346-x

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  • DOI: https://doi.org/10.1007/s10529-017-2346-x

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