{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:12:24Z","timestamp":1789999944513,"version":"4.0.1"},"reference-count":36,"publisher":"American Chemical Society (ACS)","issue":"15","license":[{"start":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T00:00:00Z","timestamp":1586217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["19-14-00115"],"award-info":[{"award-number":["19-14-00115"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The present work is focused on testing enzyme-based agents for the partial dissolution of calcium pyrophosphate (CaPPi) deposits in the cartilages and synovial fluid of patients with pyrophosphate arthropathy (CPPD disease). Previously, we suggested that inorganic pyrophosphatases (PPases) immobilized on nanodiamonds of detonation synthesis (NDs) could be appropriate for this purpose. We synthesized and characterized conjugates of NDs and PPases from Escherichia coli and Mycobacterium tuberculosis. The conjugates showed high enzymatic activity and resistance to inhibition by calcium and fluoride. Here, we tested the effectiveness of pyrophosphate (PPi) hydrolysis by the conjugates in an in vitro model system simulating the ionic composition of the synovial fluid and in the samples of synovial fluid of patients with CPPD via NMR spectroscopy. The conjugates of both PPases efficiently hydrolyzed triclinic crystalline calcium pyrophosphate (t-CPPD) in the model system. We evaluated the number of phosphorus-containing compounds in the synovial fluid, showed the possibility of PPi detection in it, and estimated the hydrolytic activity of the PPase conjugates. The soluble and immobilized PPases were able to hydrolyze a significant amount of PPi (1 mM) in the synovial fluid in short periods of time (24 h). The maximum activity was demonstrated for Mt-PPase immobilized on ND\u2013NH\u2013(CH2)6\u2013NH2 (2.24 U mg\u20131).<\/jats:p>","DOI":"10.1021\/acsomega.9b04429","type":"journal-article","created":{"date-parts":[[2020,4,7]],"date-time":"2020-04-07T10:08:08Z","timestamp":1586254088000},"page":"8579-8586","source":"Crossref","is-referenced-by-count":7,"title":["Inorganic Pyrophosphatase\u2013Nanodiamond Conjugates\nHydrolyze Pyrophosphate in Human Synovial Fluid"],"prefix":"10.1021","volume":"5","author":[{"given":"Anastasiya V.","family":"Valueva","sequence":"first","affiliation":[{"name":"Pavlov Ryazan State Medical University , , 9 Vysokovol\u2019tnaya Street , ,","place":["Ryazan, Russia, 390026"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7823-7460","authenticated-orcid":true,"given":"Roman S.","family":"Romanov","sequence":"additional","affiliation":[{"name":"Lomonosov Moscow State University , , 31, Building 5, Lomonosovsky Prospect , ,","place":["Moscow, Russia, 119991"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia S.","family":"Mariasina","sequence":"additional","affiliation":[{"name":"Lomonosov Moscow State University , , 31, Building 5, Lomonosovsky Prospect , ,","place":["Moscow, Russia, 119991"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxim S.","family":"Eliseev","sequence":"additional","affiliation":[{"name":"V.A. Nasonova Research Institute of Rheumatology , Kaschirskoe h. 34A , ,","place":["Moscow, Russia, 115522"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Rodina","sequence":"additional","affiliation":[{"name":"Lomonosov Moscow State University , , 1, Building 3, Leninskie Gory , ,","place":["Moscow, Russia, 119992"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,4,7]]},"reference":[{"key":"2026092109070913200_cit1","first-page":"32","article-title":"Update on calcium pyrophosphate\ndeposition","volume":"34","author":"Abhishek","year":"2016","journal-title":"Clin. Exp. Rheumatol."},{"key":"2026092109070913200_cit2","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1093\/rheumatology\/key092","article-title":"Inhibition\nof nucleotide pyrophosphatase\/phosphodiesterase\n1: implications for developing a calcium pyrophosphate deposition\ndisease modifying drug","volume":"57","author":"Danino","year":"2018","journal-title":"Rheumatology"},{"key":"2026092109070913200_cit3","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-016-0574-z","article-title":"The role\nof ANK in calcium pyrophosphate deposition disease","volume":"18","author":"Mitton-Fitzgerald","year":"2016","journal-title":"Curr. Rheumatol. Rep."},{"key":"2026092109070913200_cit4","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s11926-011-0230-6","article-title":"Genetics\nand mechanisms of crystal deposition in calcium pyrophosphate deposition\ndisease","volume":"14","author":"Tsui","year":"2012","journal-title":"Curr. Rheumatol. Rep."},{"key":"2026092109070913200_cit5","doi-asserted-by":"publisher","first-page":"28082","DOI":"10.1074\/jbc.271.45.28082","article-title":"Inhibition\nof calcium\npyrophosphate dihydrate crystal formation in articular cartilage vesicles\nand cartilage by phosphocitrate","volume":"271","author":"Cheung","year":"1996","journal-title":"J. Biol. Chem."},{"key":"2026092109070913200_cit6","first-page":"66","article-title":"Effects of pyrophosphatase\non dissolution of calcium pyrophosphate dihydrate crystals","volume":"18","author":"Xu","year":"1991","journal-title":"J. Rheumatol."},{"key":"2026092109070913200_cit7","doi-asserted-by":"publisher","DOI":"10.1116\/1.4934483","article-title":"Immobilization of\ninorganic pyrophosphatase on nanodiamond particles retaining its high\nenzymatic activity","volume":"10","author":"Rodina","year":"2015","journal-title":"Biointerphases"},{"key":"2026092109070913200_cit8","doi-asserted-by":"publisher","first-page":"11547","DOI":"10.1021\/acsami.5b02502","article-title":"Temperature-responsive Poly (N-isopropylacrylamide)\nmodified gold nanoparticle\u2013protein conjugates for bioactivity\nmodulation","volume":"7","author":"Liu","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026092109070913200_cit9","doi-asserted-by":"publisher","first-page":"4387","DOI":"10.1039\/C5NR07436C","article-title":"Multifunctional\nnanoparticle\u2013protein\nconjugates with controllable bioactivity and pH responsiveness","volume":"8","author":"Liu","year":"2016","journal-title":"Nanoscale"},{"key":"2026092109070913200_cit10","doi-asserted-by":"publisher","first-page":"5437","DOI":"10.1039\/C6TB01251E","article-title":"One-step synthesis\nof glycoprotein mimics in vitro: improvement of protein activity,\nstability and application in CPP hydrolysis","volume":"4","author":"Cui","year":"2016","journal-title":"J. Mater. Chem. B"},{"key":"2026092109070913200_cit11","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3109\/03009748109095305","article-title":"Measurement\nof soluble pyrophosphate in plasma and\nsynovial fluid of patients with various rheumatic diseases","volume":"10","author":"Micheli","year":"1981","journal-title":"Scand. J. Rheumatol."},{"key":"2026092109070913200_cit12","first-page":"14","article-title":"The biochemical\ncomposition of synovial\nliquid of human knee joint in normal condition (indicators of electrolytes\nand protein specter)","author":"Matveeva","year":"2012","journal-title":"Klin. Lab. Diagn."},{"key":"2026092109070913200_cit13","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1136\/ard.53.7.467","article-title":"Submicroscopic\ncrystals in osteoarthritic synovial fluids","volume":"53","author":"Swan","year":"1994","journal-title":"Ann. Rheum. 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Biotechnol."},{"key":"2026092109070913200_cit20","doi-asserted-by":"publisher","first-page":"595","DOI":"10.2174\/138620712802650522","article-title":"Application of NMR\nmetabolomics to search for human\ndisease biomarkers","volume":"15","author":"Gebregiworgis","year":"2012","journal-title":"Comb. Chem. High Throughput\nScreening"},{"key":"2026092109070913200_cit21","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1111\/j.1439-0396.2008.00822.x","article-title":"Phospholipid compositions\nof sera and synovial fluids from dog, human and horse: a comparison\nby 31P-NMR and MALDI-TOF MS","volume":"93","author":"Fuchs","year":"2009","journal-title":"J. Anim.\nPhysiol. Anim. Nutr."},{"key":"2026092109070913200_cit22","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.clinbiochem.2005.06.006","article-title":"The phosphatidylcholine\/lysophosphatidylcholine\nratio\nin human plasma is an indicator of the severity of rheumatoid arthritis:\ninvestigations by 31P NMR and MALDI-TOF MS","volume":"38","author":"Fuchs","year":"2005","journal-title":"Clin. Biochem."},{"key":"2026092109070913200_cit23","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.joca.2008.05.020","article-title":"Inorganic pyrophosphate\nas a regulator of hydroxyapatite or calcium pyrophosphate dihydrate\nmineral deposition by matrix vesicles","volume":"17","author":"Thouverey","year":"2009","journal-title":"Osteoarthritis\nCartilage"},{"key":"2026092109070913200_cit24","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/0011-5029(94)90021-3","article-title":"Crystals\nand arthritis","volume":"40","author":"McCarty","year":"1994","journal-title":"Dis. Mon."},{"key":"2026092109070913200_cit25","volume-title":"The Merck Index","author":"Budavari","year":"1996"},{"key":"2026092109070913200_cit26","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1172\/JCI108239","article-title":"Factors\naffecting the solubility\nof calcium pyrophosphate dihydrate crystals","volume":"56","author":"Bennett","year":"1975","journal-title":"J. Clin. 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Biol."},{"key":"2026092109070913200_cit32","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1042\/bj2680487","article-title":"Properties of phosphatidate\nphosphohydrolase and diacylglycerol acyltransferase activities in\nthe isolated rat heart. Effect of glucagon, ischaemia and diabetes","volume":"268","author":"Schoonderwoerd","year":"1990","journal-title":"Biochem. J."},{"key":"2026092109070913200_cit33","doi-asserted-by":"publisher","first-page":"6763","DOI":"10.1074\/jbc.M807882200","article-title":"Lipin 2 is a liver-enriched phosphatidate\nphosphohydrolase enzyme that is dynamically regulated by fasting and\nobesity in mice","volume":"284","author":"Gropler","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2026092109070913200_cit34","doi-asserted-by":"publisher","first-page":"13750","DOI":"10.1073\/pnas.1613610113","article-title":"An HD domain\nphosphohydrolase active site tailored for oxetanocin-A biosynthesis","volume":"113","author":"Bridwell-Rabb","year":"2016","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026092109070913200_cit35","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.jmb.2008.02.036","article-title":"Structural insight\ninto the mechanism of substrate specificity and catalytic activity\nof an HD-domain phosphohydrolase: the 5\u2032-deoxyribonucleotidase\nYfbR from Escherichia coli","volume":"378","author":"Zimmerman","year":"2008","journal-title":"J. Mol. Biol."},{"key":"2026092109070913200_cit36","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/0005-2744(77)90150-4","article-title":"Fluoride inhibition\nof inorganic pyrophosphatase II. Isolation and characterization of\na covalent intermediate between enzyme and entire substrate molecule","volume":"481","author":"Baykov","year":"1977","journal-title":"Biochim. Biophys. Acta Enzymol."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.9b04429","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/15\/8579\/67807826\/acsomega.9b04429.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/15\/8579\/67807826\/acsomega.9b04429.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:21:27Z","timestamp":1789996887000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/15\/8579\/619386\/Inorganic-Pyrophosphatase-Nanodiamond-Conjugates"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,7]]},"references-count":36,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2020,4,7]]},"published-print":{"date-parts":[[2020,4,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.9b04429","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,7]]}}}