{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T21:19:16Z","timestamp":1772745556389,"version":"3.50.1"},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,8,1]]},"abstract":"<jats:p>TetraPEGylated canine Hb, [SP (succinimidophenyl)-PEG5K]4-canine-Hb, with PEGylation at its four reactive cysteine residues (\u03b1111 and \u03b293) has been prepared and characterized. The hydrodynamic volume and the molecular radius of (SP-PEG5K)4-canine-Hb are intermediate to those of di- and hexaPEGylated human Hb as expected. However, the COP (colloidal osmotic pressure) of tetraPEGylated canine Hb is closer to that of hexaPEGylated human Hb than to that of diPEGylated human Hb. The O2 affinity of tetraPEGylated canine Hb is higher than that of canine Hb and comparable with that of hexaPEGylated Hb. The O2 affinity of tetraPEGylated canine Hb is not responsive to the presence of DPG (diphosphoglycerate) or chloride, but it retains almost full response to L-35, an allosteric effector that interacts at the \u03b1\u03b1-end of the central cavity. The tetraPEGylated canine Hb is vasoinactive in hamster in 10% top load infusion studies. It is also essentially non-hypertensive in an extreme exchange haemodilution protocol in hamster just as di- and hexaPEGylated human Hb. The O2 delivery by tetraPEGylated canine Hb is comparable with that of hexaPEGylated Hb but not as efficient as diPEGylated Hb. These results demonstrate that PEGylation-induced solution properties of PEG [poly(ethylene glycol)]\u2013Hb conjugates are dictated by the level and chemistry of PEGylation and the interplay of these plays a critical role in tissue oxygenation. The studies imply the need to establish the right level (and\/or pattern) of PEGylation and O2 affinity of Hb\u2013PEG adducts in designing O2-carrying plasma volume expanders, and this remains the primary challenge in the design of PEGylated Hb as blood substitutes.<\/jats:p>","DOI":"10.1042\/bj20070238","type":"journal-article","created":{"date-parts":[[2007,7,16]],"date-time":"2007-07-16T12:40:35Z","timestamp":1184589635000},"page":"503-511","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Non-hypertensive tetraPEGylated canine haemoglobin: correlation between PEGylation, O2 affinity and tissue oxygenation"],"prefix":"10.1042","volume":"405","author":[{"given":"Seetharama\u00a0A.","family":"Acharya","sequence":"first","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, U.S.A."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vivek\u00a0N.","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, U.S.A."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirmala\u00a0Devi","family":"Kanika","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, U.S.A."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy\u00a0G.","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California at San Diego, La Jolla, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Intaglietta","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, University of California at San Diego, La Jolla, CA, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Belur\u00a0N.","family":"Manjula","sequence":"additional","affiliation":[{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, U.S.A."},{"name":"Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2007,7,13]]},"reference":[{"key":"2021112213405528100_B1","doi-asserted-by":"crossref","first-page":"12128","DOI":"10.1074\/jbc.273.20.12128","article-title":"Arterial blood pressure responses to cell-free hemoglobin solutions and the reaction with nitric oxide","volume":"273","author":"Rohlfs","year":"1998","journal-title":"J. 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