Ukr.Biochem.J. 2019; Volume 91, Issue 4, Jul-Aug, pp. 70-77


Calculations of supramolecular structures of peptidylboronic acid (bortezomib) with ABO blood system antigen

A. D. Kustovska1, S. V. Prymachenko1, Zh. M. Minchenko2,
T. F. Liubarets2, O. O. Dmytrenko2

1National Aviation University, Kyiv, Ukraine;
2SI “National Research Center for Radiation Medicine of National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine

Received: 08 April 2019; Accepted: 17 May 2019

Peptidylboronic acids have recently become widespread as effective drugs for cancer treatment. Howe­ver, the use of these drugs is often accompanied by negative side effects associated with the phenotypic affiliation to the ABO system. Therefore, it is important to determine the role of pharmaco-chemical charac­teristics of antigens of ABO system and therapeutic agents (for example, bortezomib) in the selection of individualized therapies for patients with chronic lymphoproliferative neoplasms. The expediency and efficiency of bortezomib use for patients with plasma cell myeloma depen­ding on the phenotype affiliation to the ABO system were evaluated. Efficiency of plasma cell myeloma therapy was analyzed in 104 patients who received treatment according to clinical protocols. Dependence of the duration of remission in performance of standard polychemotherapy was researched. Calculation of energy parameters and geomet­ry of probable supramolecular structures of peptidylboronic (bortezomib) and boric acids with antigens of the ABO blood system was performed in the HyperChem 8.07 software package. It was demonstrated that the ability of antigens to form supramolecular complexes with bortezomib varies in the series: B1 >> 01 > A1, which is in line with the results of clinical researches. It was assumed that in case of patients with В blood group secondary process (interaction of bortezomib with carbohydrate antigen) is energetically more beneficial than the main process (inhibition of proteasome), while for patients with O and A groups, equilibrium is shifted toward the main reaction, which results in the therapeutic effect of the drug.

Keywords: , , , ,


  1. Hall DG.(Ed.). Boronic acids: preparation, applications in organic synthesis and medicine. John Wiley & Sons, 2006. 549 p. CrossRef
  2. Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011 Mar;11(3):239-53. PubMed, PubMedCentral, CrossRef
  3. Huber EM, Heinemeyer W, Groll M. Bortezomib-resistant mutant proteasomes: structural and biochemical evaluation with carfilzomib and ONX 0914. Structure. 2015 Feb 3;23(2):407-17.  PubMed, CrossRef
  4. Harshbarger W, Miller C, Diedrich C, Sacchettini J. Crystal structure of the human 20S proteasome in complex with carfilzomib. Structure. 2015 Feb 3;23(2):418-24. PubMed, CrossRef
  5. Pitcher DS, de Mattos-Shipley K, Tzortzis K, Auner HW, Karadimitris A, Kleijnen MF. Bortezomib Amplifies Effect on Intracellular Proteasomes by Changing Proteasome Structure. EBioMedicine. 2015 May 28;2(7):642-8. PubMed, PubMedCentral, CrossRef
  6. Chandra A, Wang L, Young T, Zhong L, Tseng WJ, Levine MA, Cengel K, Liu XS, Zhang Y, Pignolo RJ, Qin L. Proteasome inhibitor bortezomib is a novel therapeutic agent for focal radiation-induced osteoporosis. FASEB J. 2018 Jan;32(1):52-62. PubMed, PubMedCentral, CrossRef
  7. Spoerke ED, Jones B, Martinez A, Small L, Wheeler D, Wheeler J, Bacgand G. Molecular Biomimicry: Imitating Nature in Responsive Supramolecular Materials.  No. SAND2017-6605C. Sandia National Lab.(SNL-NM), Albuquerque, NM (United States), 2017.
  8. Godoy-Gallardo M,  York-Duran MJ, Hosta-Rigau L. Recent Progress in Micro/Nanoreactors toward the Creation of Artificial Organelles. Adv Healthc Mater. 2018;7(5):1700917. CrossRef
  9. Pizer R. Boron acid complexation reactions with polyols and α-hydroxy carboxylic acids: Equilibria, reaction mechanisms, saccharide recognition. Inorganica Chim Acta. 2017;467:194-197.  CrossRef
  10. Furikado Y, Nagahata T, Okamoto T, Sugaya T, Iwatsuki S, Inamo M, Takagi HD, Odani A, Ishihara K. Universal reaction mechanism of boronic acids with diols in aqueous solution: kinetics and the basic concept of a conditional formation constant. Chemistry. 2014 Oct 6;20(41):13194-202. PubMed, CrossRef
  11. Goy A, Gilles F. Update on the proteasome inhibitor bortezomib in hematologic malignancies. Clin Lymphoma. 2004 Mar;4(4):230-7. PubMed, CrossRef
  12. Hasinoff BB, Patel D, Wu X. Molecular Mechanisms of the Cardiotoxicity of the Proteasomal-Targeted Drugs Bortezomib and Carfilzomib. Cardiovasc Toxicol. 2017 Jul;17(3):237-250. PubMed, CrossRef
  13. Guglielmi V, Nowis D, Tinelli M, Malatesta M, Paoli L, Marini M, Manganotti P, Sadowski R, Wilczynski GM, Meneghini V, Tomelleri G, Vattemi G. Bortezomib-Induced Muscle Toxicity in Multiple Myeloma. J Neuropathol Exp Neurol. 2017 Jul 1;76(7):620-630. PubMed, CrossRef
  14. Kanayama N, Kitano H. Interfacial recognition of sugars by boronic acid-carrying self-assembled monolayer. Langmuir. 2000;16(2):577-583. CrossRef
  15. Zhang XT, Dong HL, Niu ZL, Xu JM, Wang DY, Tong H, Jiang XZ,  Zhu MF. Loading and Controlled Releasing of Anti-cancer Drug Bortezomib by Glucose-Containing Diblock Copolymer. Chinese Materials Conference. Springer, Singapore, 2017: 871-880. CrossRef
  16. Lorand JP, Edwards JO. Polyol complexes and structure of the benzeneboronate ion. J Org Chem. 1959;24(6):769-774. CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.