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Conjugates for use in peptide therapeutics: A systematic review and meta-analysis

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  • Ashan Wijesinghe
  • Sarika Kumari
  • Valerie Booth

Abstract

While peptides can be excellent therapeutics for several conditions, their limited in vivo half-lives have been a major bottleneck in the development of therapeutic peptides. Conjugating the peptide to an inert chemical moiety is a strategy that has repeatedly proven to be successful in extending the half-life of some therapeutics. This systematic review and meta-analysis was conducted to examine the available literature and assess it in an unbiased manner to determine which conjugates, both biological and synthetic, provide the greatest increase in therapeutic peptide half-life. Systematic searches run on PubMed, Scopus and SciFinder databases resulted in 845 studies pertaining to the topic, 16 of these were included in this review after assessment against pre-specified inclusion criteria registered on PROSPERO (#CRD42020222579). The most common reasons for exclusion were non-IV administration and large peptide size. Of the 16 studies that were included, a diverse suite of conjugates that increased half-life from 0.1 h to 33.57 h was identified. Amongst these peptides, the largest increase in half-life was seen when conjugated with glycosaminoglycans. A meta-analysis of studies that contained fatty acid conjugates indicated that acylation contributed to a statistically significant extension of half-life. Additionally, another meta-analysis followed by a sensitivity analysis suggested that conjugation with specifically engineered recombinant peptides might contribute to a more efficient extension of peptide half-life as compared to PEGylation. Moreover, we confirmed that while polyethylene glycol is a good synthetic conjugate, its chain length likely has an impact on its effectiveness in extending half-life. Furthermore, we found that most animal studies do not include as much detail when reporting findings as compared to human studies. Inclusion of additional experimental detail on aspects such as independent assessment and randomization may be an easily accomplished strategy to drive more conjugated peptides towards clinical studies.

Suggested Citation

  • Ashan Wijesinghe & Sarika Kumari & Valerie Booth, 2022. "Conjugates for use in peptide therapeutics: A systematic review and meta-analysis," PLOS ONE, Public Library of Science, vol. 17(3), pages 1-19, March.
  • Handle: RePEc:plo:pone00:0255753
    DOI: 10.1371/journal.pone.0255753
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    References listed on IDEAS

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    1. Alessandro Zorzi & Simon J. Middendorp & Jonas Wilbs & Kaycie Deyle & Christian Heinis, 2017. "Acylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides," Nature Communications, Nature, vol. 8(1), pages 1-9, December.
    2. Alessandro Liberati & Douglas G Altman & Jennifer Tetzlaff & Cynthia Mulrow & Peter C Gøtzsche & John P A Ioannidis & Mike Clarke & P J Devereaux & Jos Kleijnen & David Moher, 2009. "The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration," PLOS Medicine, Public Library of Science, vol. 6(7), pages 1-28, July.
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