{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:10:52Z","timestamp":1790647852377,"version":"4.1.0"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2017,1,30]],"date-time":"2017-01-30T00:00:00Z","timestamp":1485734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The demand has increased for sophisticated molecular tools with improved detection limits. Such molecules should be simple in structure, yet stable enough for clinical applications. Nucleic acid aptamers (NAAs) represent a class of molecules able to meet this demand. In particular, aptamers, a class of small nucleic acid ligands that are composed of single-stranded modified\/unmodified RNA\/DNA molecules, can be evolved from a complex library using Systematic Evolution of Ligands by EXponential enrichment (SELEX) against almost any molecule. Since its introduction in 1990, in stages, SELEX technology has itself undergone several modifications, improving selection and broadening the repertoire of targets. This review summarizes these milestones that have pushed the field forward, allowing researchers to generate aptamers that can potentially be applied as therapeutic and diagnostic agents.<\/jats:p>","DOI":"10.3390\/molecules22020215","type":"journal-article","created":{"date-parts":[[2017,1,30]],"date-time":"2017-01-30T11:36:30Z","timestamp":1485776190000},"page":"215","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Evolution of Complex Target SELEX to Identify Aptamers against Mammalian Cell-Surface Antigens"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-4613","authenticated-orcid":false,"given":"Prabodhika","family":"Mallikaratchy","sequence":"first","affiliation":[{"name":"Department of Chemistry, Lehman College, The City University of New York, 250 Bedford Park Blvd. West, Bronx, NY 10468, USA"},{"name":"Ph.D. Programs in Chemistry and Biochemistry, CUNY Graduate Center 365 Fifth Avenue, New York, NY 10016, USA"},{"name":"Ph.D. Program in Molecular, Cellular and Developmental Biology, CUNY Graduate Center 365 Fifth Avenue, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"343fs310","DOI":"10.1126\/scitranslmed.aaf8590","article-title":"Measure for measure: Biomarker standards and transparency","volume":"8","author":"FitzGerald","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1097\/COH.0b013e32833ed177","article-title":"What are biomarkers?","volume":"5","author":"Strimbu","year":"2010","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17854","DOI":"10.1038\/srep17854","article-title":"The assessment of the readiness of molecular biomarker-based mobile health technologies for healthcare applications","volume":"5","author":"Qin","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ddtec.2016.11.003","article-title":"Pharmacogenomics in the age of personalized medicine","volume":"21\u201322","author":"Dickmann","year":"2016","journal-title":"Drug Discov. Today Technol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Jain, K.K. (2010). The Handbook of Biomarkers, Springer.","DOI":"10.1007\/978-1-60761-685-6"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1089\/nat.2016.0632","article-title":"Aptamers: Promising tools for the detection of circulating tumor cells","volume":"26","author":"Hassan","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1038\/nrd3141","article-title":"Aptamers as therapeutics","volume":"9","author":"Keefe","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1093\/clinchem\/45.9.1628","article-title":"Aptamers: An emerging class of molecules that rival antibodies in diagnostics","volume":"45","author":"Jayasena","year":"1999","journal-title":"Clin. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/1074-5521(95)90023-3","article-title":"Let\u2019s get specific: The relationship between specificity and affinity","volume":"2","author":"Eaton","year":"1995","journal-title":"Chem. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1172\/JCI11325","article-title":"Developing aptamers into therapeutics","volume":"106","author":"White","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2957","DOI":"10.1158\/1535-7163.MCT-06-0172","article-title":"Discovery and development of anticancer aptamers","volume":"5","author":"Ireson","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5757","DOI":"10.1093\/nar\/gkh862","article-title":"Application of locked nucleic acids to improve aptamer in vivo stability and targeting function","volume":"32","author":"Schmidt","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1007\/s11095-004-7676-4","article-title":"Pharmacokinetics and biodistribution of novel aptamer compositions","volume":"21","author":"Healy","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1089\/oli.1.2000.10.63","article-title":"Anti-l-selectin aptamers: Binding characteristics, pharmacokinetic parameters, and activity against an intravascular target in vivo","volume":"10","author":"Watson","year":"2000","journal-title":"Antisense Nucleic Acid Drug Dev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.7150\/thno.15666","article-title":"Generating cell targeting aptamers for nanotheranostics using cell-selex","volume":"6","author":"Lyu","year":"2016","journal-title":"Theranostics"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"16014","DOI":"10.1038\/mtm.2016.14","article-title":"From selection hits to clinical leads: Progress in aptamer discovery","volume":"5","author":"Maier","year":"2016","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1089\/nat.2015.0573","article-title":"Fit for the eye: Aptamers in ocular disorders","volume":"26","author":"Drolet","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1161\/ATVBAHA.115.300131","article-title":"Modulation of the coagulation cascade using aptamers","volume":"35","author":"Woodruff","year":"2015","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"748913","DOI":"10.1155\/2012\/748913","article-title":"Challenges and opportunities for small molecule aptamer development","volume":"2012","author":"McKeague","year":"2012","journal-title":"J. Nucleic Acids"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Catuogno, S., Esposito, C.L., and de Franciscis, V. (2016). Aptamer-mediated targeted delivery of therapeutics: An update. Pharmaceuticals, 9.","DOI":"10.3390\/ph9040069"},{"key":"ref_21","first-page":"500","article-title":"Aptamer-mediated selective delivery of short RNA therapeutics in cancer cells","volume":"10","author":"Esposito","year":"2014","journal-title":"J. RNAi Gene Silenc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"5700","DOI":"10.1093\/nar\/gkg764","article-title":"In vitro selection of molecular beacons","volume":"31","author":"Rajendran","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1158\/1535-7163.MCT-15-0201-T","article-title":"Gene knockdown by epcam aptamer-siRNA chimeras suppresses epithelial breast cancers and their tumor-initiating cells","volume":"14","author":"Hamar","year":"2015","journal-title":"Mol. Cancer Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1038\/nbt1223","article-title":"Cell type-specific delivery of sirnas with aptamer-sirna chimeras","volume":"24","author":"McNamara","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e289","DOI":"10.1038\/mtna.2016.5","article-title":"Aptamer-miRNA-212 conjugate sensitizes NSCLC cells to TRAIL","volume":"5","author":"Iaboni","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/978-1-4939-3112-5_16","article-title":"Aptamer-miRNA conjugates for cancer cell-targeted delivery","volume":"1364","author":"Esposito","year":"2016","journal-title":"Methods Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/344467a0","article-title":"Selection in vitro of an RNA enzyme that specifically cleaves single-stranded DNA","volume":"344","author":"Robertson","year":"1990","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1126\/science.2200121","article-title":"Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage t4 DNA polymerase","volume":"249","author":"Tuerk","year":"1990","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/346818a0","article-title":"In vitro selection of rna molecules that bind specific ligands","volume":"346","author":"Ellington","year":"1990","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.cbpa.2006.03.015","article-title":"Aptamer therapeutics advance","volume":"10","author":"Lee","year":"2006","journal-title":"Curr. Opin. Chem. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"VEGF Inhibition Study in Ocular Neovascularization (V.I.S.I.O.N.) Clinical Trial Group, Chakravarthy, U., Adamis, A.P., Cunningham, E.T., Goldbaum, M., Guyer, D.R., Katz, B., and Patel, M. (2006). Year 2 efficacy results of 2 randomized controlled clinical trials of pegaptanib for neovascular age-related macular degeneration. Ophthalmology, 113, 1508.e1\u20131508.e25.","DOI":"10.1016\/j.ophtha.2006.02.064"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrd1955","article-title":"Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease","volume":"5","author":"Ng","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.ejps.2012.10.014","article-title":"Therapeutic RNA aptamers in clinical trials","volume":"48","author":"Sundaram","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1093\/nar\/gkl388","article-title":"Aptamer mediated siRNA delivery","volume":"34","author":"Chu","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/nbt.1560","article-title":"Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors","volume":"27","author":"Dassie","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1038\/mt.2014.117","article-title":"Targeted inhibition of prostate cancer metastases with an RNA aptamer to prostate-specific membrane antigen","volume":"22","author":"Dassie","year":"2014","journal-title":"Mol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1021\/ar700142z","article-title":"Complex target selex","volume":"41","author":"Shamah","year":"2008","journal-title":"Accounts Chem. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.1073\/pnas.95.6.2902","article-title":"High affinity ligands from in vitro selection: Complex targets","volume":"95","author":"Morris","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"48644","DOI":"10.1074\/jbc.M104651200","article-title":"Tenascin-C aptamers are generated using tumor cells and purified protein","volume":"276","author":"Hicke","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e182","DOI":"10.1038\/mtna.2014.32","article-title":"Oligonucleotide aptamers: New tools for targeted cancer therapy","volume":"3","author":"Sun","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1038\/mtna.2012.14","article-title":"An RNA alternative to human transferrin: A new tool for targeting human cells","volume":"1","author":"Wilner","year":"2012","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"15416","DOI":"10.1073\/pnas.2136683100","article-title":"A tenascin-C aptamer identified by tumor cell selex: Systematic evolution of ligands by exponential enrichment","volume":"100","author":"Daniels","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11838","DOI":"10.1073\/pnas.0602615103","article-title":"Aptamers evolved from live cells as effective molecular probes for cancer study","volume":"103","author":"Shangguan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Tan, W., and Fang, X. (2015). Aptamers Selected by Cell-SELEX for Theranostics, Springer.","DOI":"10.1007\/978-3-662-46226-3"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1373\/clinchem.2006.083246","article-title":"Aptamers evolved from cultured cancer cells reveal molecular differences of cancer cells in patient samples","volume":"53","author":"Shangguan","year":"2007","journal-title":"Clin. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1021\/pr700894d","article-title":"Cell-specific aptamer probes for membrane protein elucidation in cancer cells","volume":"7","author":"Shangguan","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"384","DOI":"10.3109\/07357909709039744","article-title":"Flow cytometry: Recent advances in diagnosis and monitoring of leukemia","volume":"15","author":"Jennings","year":"1997","journal-title":"Cancer Investig."},{"key":"ref_48","first-page":"579","article-title":"Identification and functional characterization of mononuclear cells by flow cytometry","volume":"113","author":"Bray","year":"1989","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/0090-1229(89)90192-X","article-title":"Procedural guidelines for performing immunophenotyping by flow cytometry","volume":"52","author":"Landay","year":"1989","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.1021\/ac070189y","article-title":"Selection of aptamers for molecular recognition and characterization of cancer cells","volume":"79","author":"Tang","year":"2007","journal-title":"Anal. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1074\/mcp.M700026-MCP200","article-title":"Aptamer directly evolved from live cells recognizes membrane bound immunoglobin heavy mu chain in Burkitt\u2019s lymphoma cells","volume":"6","author":"Mallikaratchy","year":"2007","journal-title":"Mol. Cell. Proteom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3914","DOI":"10.1002\/anie.201510786","article-title":"Intercellular connections related to cell-cell crosstalk specifically recognized by an aptamer","volume":"55","author":"Zhang","year":"2016","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4941","DOI":"10.1021\/acs.analchem.5b00637","article-title":"Evolution of DNA aptamers through in vitro metastatic-cell-based systematic evolution of ligands by exponential enrichment for metastatic cancer recognition and imaging","volume":"87","author":"Li","year":"2015","journal-title":"Anal. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4923","DOI":"10.1158\/0008-5472.CAN-12-4556","article-title":"Aptamer identification of brain tumor-initiating cells","volume":"73","author":"Kim","year":"2013","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1002\/ijc.27936","article-title":"Cell-based selection provides novel molecular probes for cancer stem cells","volume":"132","author":"Sefah","year":"2013","journal-title":"Int. J. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1756-8722-7-5","article-title":"Developing aptamer probes for acute myelogenous leukemia detection and surface protein biomarker discovery","volume":"7","author":"Yang","year":"2014","journal-title":"J. Hematol. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Cerchia, L., Esposito, C.L., Jacobs, A.H., Tavitian, B., and de Franciscis, V. (2009). Differential SELEX in human glioma cell lines. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007971"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1038\/nprot.2010.163","article-title":"Fluorescence-activated cell sorting for aptamer selex with cell mixtures","volume":"5","author":"Mayer","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1002\/chem.200701330","article-title":"Cell-specific internalization study of an aptamer from whole cell selection","volume":"14","author":"Xiao","year":"2008","journal-title":"Chemistry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1073\/pnas.1311778111","article-title":"In vitro selection with artificial expanded genetic information systems","volume":"111","author":"Sefah","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/cr.2015.7","article-title":"Characterization and target identification of a DNA aptamer that labels pluripotent stem cells","volume":"25","author":"Hou","year":"2015","journal-title":"Cell Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"6319","DOI":"10.1093\/nar\/gks294","article-title":"Delivery of chemo-sensitizing siRNAs to HER2+-breast cancer cells using RNA aptamers","volume":"40","author":"Thiel","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e365","DOI":"10.1038\/mtna.2016.73","article-title":"Targeting insulin receptor with a novel internalizing aptamer","volume":"5","author":"Iaboni","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ab.2016.08.007","article-title":"Ligand-guided selection of aptamers against T-cell receptor-cluster of differentiation 3 (TCR-CD3) expressed on jurkat.E6 cells","volume":"512","author":"Zumrut","year":"2016","journal-title":"Anal. Biochem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1089\/nat.2016.0611","article-title":"Ligand-guided selection of target-specific aptamers: A screening technology for identifying specific aptamers against cell-surface proteins","volume":"26","author":"Zumrut","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e201","DOI":"10.1038\/mtna.2014.49","article-title":"Nucleic acid ligands with protein-like side chains: Modified aptamers and their use as diagnostic and therapeutic agents","volume":"3","author":"Rohloff","year":"2014","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Gold, L., Ayers, D., Bertino, J., Bock, C., Bock, A., Brody, E.N., Carter, J., Dalby, A.B., Eaton, B.E., and Fitzwater, T. (2010). Aptamer-based multiplexed proteomic technology for biomarker discovery. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0015004"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8321","DOI":"10.1021\/bi300471d","article-title":"X-aptamers: A bead-based selection method for random incorporation of druglike moieties onto next-generation aptamers for enhanced binding","volume":"51","author":"He","year":"2012","journal-title":"Biochemistry"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/9780470559277.ch140233","article-title":"Selma: Selection with modified aptamers","volume":"7","author":"Temme","year":"2015","journal-title":"Curr. Protoc. Chem. Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1726","DOI":"10.1021\/ja411212q","article-title":"High temperature selma: Evolution of DNA-supported oligomannose clusters which are tightly recognized by HIV bnab 2G12","volume":"136","author":"Temme","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"10971","DOI":"10.1002\/anie.201503652","article-title":"A versatile approach towards nucleobase-modified aptamers","volume":"54","author":"Tolle","year":"2015","journal-title":"Angew. Chem. Int. Ed. Engl."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/2\/215\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:27:16Z","timestamp":1760207236000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/22\/2\/215"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,30]]},"references-count":71,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2017,2]]}},"alternative-id":["molecules22020215"],"URL":"https:\/\/doi.org\/10.3390\/molecules22020215","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,30]]}}}