Non-hypertensive tetraPEGylated canine haemoglobin: Correlation between PEGylation, O2 affinity and tissue oxygenation

Seetharama A. Acharya, Vivek N. Acharya, Nirmala Devi Kanika, Amy G. Tsai, Marcos Intaglietta, Belur N. Manjula

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

TetraPEGylated canine Hb, [SP (succinimidophenyl)-PEG5K] 4-canine-Hb, with PEGylation at its four reactive cysteine residues (α111 and β93) 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 αα-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)]-Hb 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-PEG adducts in designing O2-carrying plasma volume expanders, and this remains the primary challenge in the design of PEGylated Hb as blood substitutes.

Original languageEnglish (US)
Pages (from-to)503-511
Number of pages9
JournalBiochemical Journal
Volume405
Issue number3
DOIs
StatePublished - Aug 1 2007

Fingerprint

Oxygenation
Polyethylene glycols
Canidae
Hemoglobins
Plasma Substitutes
Tissue
Blood Substitutes
Cysteine
Chlorides
Hydrodynamics
Cricetinae
L 35
Hemodilution
Ethylene Glycol
Osmotic Pressure
PEG-hemoglobin

Keywords

  • Blood
  • Non-hypertensive tetraPEGylated canine haemoglobin
  • O affinity
  • PEGylation
  • Poly(ethylene glycol) (PEG)
  • Tissue oxygenation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Acharya, S. A., Acharya, V. N., Kanika, N. D., Tsai, A. G., Intaglietta, M., & Manjula, B. N. (2007). Non-hypertensive tetraPEGylated canine haemoglobin: Correlation between PEGylation, O2 affinity and tissue oxygenation. Biochemical Journal, 405(3), 503-511. https://doi.org/10.1042/BJ20070238

Non-hypertensive tetraPEGylated canine haemoglobin : Correlation between PEGylation, O2 affinity and tissue oxygenation. / Acharya, Seetharama A.; Acharya, Vivek N.; Kanika, Nirmala Devi; Tsai, Amy G.; Intaglietta, Marcos; Manjula, Belur N.

In: Biochemical Journal, Vol. 405, No. 3, 01.08.2007, p. 503-511.

Research output: Contribution to journalArticle

Acharya, SA, Acharya, VN, Kanika, ND, Tsai, AG, Intaglietta, M & Manjula, BN 2007, 'Non-hypertensive tetraPEGylated canine haemoglobin: Correlation between PEGylation, O2 affinity and tissue oxygenation', Biochemical Journal, vol. 405, no. 3, pp. 503-511. https://doi.org/10.1042/BJ20070238
Acharya, Seetharama A. ; Acharya, Vivek N. ; Kanika, Nirmala Devi ; Tsai, Amy G. ; Intaglietta, Marcos ; Manjula, Belur N. / Non-hypertensive tetraPEGylated canine haemoglobin : Correlation between PEGylation, O2 affinity and tissue oxygenation. In: Biochemical Journal. 2007 ; Vol. 405, No. 3. pp. 503-511.
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