Skip to main content
Journal cover image

Site-Specific Zwitterionic Polymer Conjugates of a Protein Have Long Plasma Circulation.

Publication ,  Journal Article
Bhattacharjee, S; Liu, W; Wang, W-H; Weitzhandler, I; Li, X; Qi, Y; Liu, J; Pang, Y; Hunt, DF; Chilkoti, A
Published in: Chembiochem : a European journal of chemical biology
November 2015

Many proteins suffer from suboptimal pharmacokinetics (PK) that limit their utility as drugs. The efficient synthesis of polymer conjugates of protein drugs with tunable PK to optimize their in vivo efficacy is hence critical. We report here the first study of the in vivo behavior of a site-specific conjugate of a zwitterionic polymer and a protein. To synthesize the conjugate, we first installed an initiator for atom-transfer radical polymerization (ATRP) at the N terminus of myoglobin (Mb-N-Br). Subsequently, in situ ATRP was carried out in aqueous buffer to grow an amine-functionalized polymer from Mb-N-Br. The cationic polymer was further derivatized to two zwitterionic polymers by treating the amine groups of the cationic polymer with iodoacetic acid to obtain poly(carboxybetaine methacrylate) with a one-carbon spacer (PCBMA; C1 ), and sequentially with 3-iodopropionic acid and iodoacetic acid to obtain PCBMA(mix) with a mixture of C1 and C2 spacers. The Mb-N-PCBMA polymer conjugates had a longer in vivo plasma half-life than a PEG-like comb polymer conjugate of similar molecular weights (MW). The structure of the zwitterion plays a role in controlling the in vivo behavior of the conjugate, as the PCBMA conjugate with a C1 spacer had significantly longer plasma circulation than the conjugate with a mixture of C1 and C2 spacers.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Chembiochem : a European journal of chemical biology

DOI

EISSN

1439-7633

ISSN

1439-4227

Publication Date

November 2015

Volume

16

Issue

17

Start / End Page

2451 / 2455

Related Subject Headings

  • ROC Curve
  • Polymethacrylic Acids
  • Polymers
  • Polymerization
  • Organic Chemistry
  • Myoglobin
  • Molecular Weight
  • Iodoacetic Acid
  • Half-Life
  • Free Radicals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Bhattacharjee, S., Liu, W., Wang, W.-H., Weitzhandler, I., Li, X., Qi, Y., … Chilkoti, A. (2015). Site-Specific Zwitterionic Polymer Conjugates of a Protein Have Long Plasma Circulation. Chembiochem : A European Journal of Chemical Biology, 16(17), 2451–2455. https://doi.org/10.1002/cbic.201500439
Bhattacharjee, Somnath, Wenge Liu, Wei-Han Wang, Isaac Weitzhandler, Xinghai Li, Yizhi Qi, Jinyao Liu, Yan Pang, Donald F. Hunt, and Ashutosh Chilkoti. “Site-Specific Zwitterionic Polymer Conjugates of a Protein Have Long Plasma Circulation.Chembiochem : A European Journal of Chemical Biology 16, no. 17 (November 2015): 2451–55. https://doi.org/10.1002/cbic.201500439.
Bhattacharjee S, Liu W, Wang W-H, Weitzhandler I, Li X, Qi Y, et al. Site-Specific Zwitterionic Polymer Conjugates of a Protein Have Long Plasma Circulation. Chembiochem : a European journal of chemical biology. 2015 Nov;16(17):2451–5.
Bhattacharjee, Somnath, et al. “Site-Specific Zwitterionic Polymer Conjugates of a Protein Have Long Plasma Circulation.Chembiochem : A European Journal of Chemical Biology, vol. 16, no. 17, Nov. 2015, pp. 2451–55. Epmc, doi:10.1002/cbic.201500439.
Bhattacharjee S, Liu W, Wang W-H, Weitzhandler I, Li X, Qi Y, Liu J, Pang Y, Hunt DF, Chilkoti A. Site-Specific Zwitterionic Polymer Conjugates of a Protein Have Long Plasma Circulation. Chembiochem : a European journal of chemical biology. 2015 Nov;16(17):2451–2455.
Journal cover image

Published In

Chembiochem : a European journal of chemical biology

DOI

EISSN

1439-7633

ISSN

1439-4227

Publication Date

November 2015

Volume

16

Issue

17

Start / End Page

2451 / 2455

Related Subject Headings

  • ROC Curve
  • Polymethacrylic Acids
  • Polymers
  • Polymerization
  • Organic Chemistry
  • Myoglobin
  • Molecular Weight
  • Iodoacetic Acid
  • Half-Life
  • Free Radicals