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Anticancer protein that bites its tail is more effective

Cyclized protein-polymer conjugate works better than linear counterparts

by Stu Borman
January 29, 2018 | A version of this story appeared in Volume 96, Issue 5

Credit: J. Am. Chem. Soc.
Cyclized interferon-polymer conjugate (top) and a linear counterpart.
Comparison of two conjugate ribbon structures, one cyclized and one not.
Credit: J. Am. Chem. Soc.
Cyclized interferon-polymer conjugate (top) and a linear counterpart.

Cyclizing the termini of protein drugs can improve their pharmaceutical properties modestly, and adding polymers to protein drugs can improve their ability to last a long time in the bloodstream. But anticancer protein-polymer conjugates are often too bulky to enter tumors deeply. Researchers now find that cyclization and polymer conjugation work better together than alone. Hua Lu of Peking University and coworkers cyclized a conjugate of the anticancer protein interferon and an amino acid polymer. Compared with noncyclized conjugates, the cyclized agents have longer circulation half-life, remarkably higher retention time in tumors, and deeper tumor penetration in mice (J. Am. Chem. Soc. 2017, DOI: 10.1021/jacs.7b13017). It also inhibits tumor progression and extends survival in mice bearing grafted human tumors, while minimizing liver-damaging side effects. The researchers have not confirmed those findings in people yet, but they believe that their study provides the best evidence so far that cyclizing protein-polymer conjugates is a valuable therapeutic approach warranting further preclinical study.


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