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The ADN\u2010PEG conjugates showed null to moderate toxicity in murine macrophages and <jats:bold>12c<\/jats:bold> was active against <jats:italic>Mycobacterium aurum<\/jats:italic> growth (MIC\u00a0=\u00a062.5\u00a0mg\/L). The conjugates were not active against <jats:italic>Mycobacterium bovis<\/jats:italic> BCG. Conjugates <jats:bold>10b<\/jats:bold> and <jats:bold>11b<\/jats:bold> exhibited high water solubility with solubility values of 1.22 and 1.18\u2009mg\/ml, respectively, in phosphate buffer solutions at pH\u00a06.8. Further, <jats:bold>10b<\/jats:bold> and <jats:bold>11b<\/jats:bold> induced a significant increase in cAMP accumulation in RAW264.7 cells comparable with that induced by adenosine. Analogues <jats:bold>10c<\/jats:bold>, <jats:bold>11c<\/jats:bold> and <jats:bold>12c<\/jats:bold> were docked to the A<jats:sub>1<\/jats:sub>, A<jats:sub>2A<\/jats:sub>, A<jats:sub>2B<\/jats:sub> and A<jats:sub>3<\/jats:sub> adenosine receptors (ARs) using crystal\u2010structures and homology models. ADN\u2010PEG\u2010conjugates bearing chains with up to five ethyleneoxy units could be well accommodated within the binding sites of A<jats:sub>1<\/jats:sub>, A<jats:sub>2A<\/jats:sub> and A<jats:sub>3<\/jats:sub> ARs. Docking studies showed that compound <jats:bold>10b<\/jats:bold> and <jats:bold>11b<\/jats:bold> were the best A<jats:sub>2A<\/jats:sub> receptor binders of the series, whereas <jats:bold>12c<\/jats:bold> was the best binder for A<jats:sub>1<\/jats:sub> AR. In summary, introduction of hydrophilic PEG substituents at the C2 of adenine ring significantly improved water solubility and did not affect AR binding properties of the ADN\u2010PEG conjugates.<\/jats:p>","DOI":"10.1111\/cbdd.14128","type":"journal-article","created":{"date-parts":[[2022,8,4]],"date-time":"2022-08-04T07:09:33Z","timestamp":1659596973000},"page":"340-349","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>C2<\/scp>\u2010linked alkynyl poly\u2010ethylene glycol(<scp>PEG<\/scp>) adenosine conjugates as water\u2010soluble adenosine receptor agonists"],"prefix":"10.1111","volume":"101","author":[{"given":"Lindsay","family":"Ferguson","sequence":"first","affiliation":[{"name":"School of Science University of the West of Scotland  Paisley UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasrin Shokrzadeh","family":"Madieh","sequence":"additional","affiliation":[{"name":"Leicester School of Pharmacy De Montfort University  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Vaideanu","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Schatzlein","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Festa","sequence":"additional","affiliation":[{"name":"Leicester School of Allied Health Sciences De Montfort University  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2337-3523","authenticated-orcid":false,"given":"Harprit","family":"Singh","sequence":"additional","affiliation":[{"name":"Leicester School of Allied Health Sciences De Montfort University  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey","family":"Wells","sequence":"additional","affiliation":[{"name":"UCL School of Pharmacy University College London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-9295","authenticated-orcid":false,"given":"Sanjib","family":"Bhakta","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Institute of Structural and Molecular Biology Birkbeck, University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8661-2910","authenticated-orcid":false,"given":"Federico","family":"Brucoli","sequence":"additional","affiliation":[{"name":"Leicester School of Pharmacy De Montfort University  Leicester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00090a017"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv082"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-017-9591-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300087j"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg444"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.113.008540"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-6497-0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12350-012-9671-1"},{"volume-title":"Amber 2022","year":"2022","author":"Case D. 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