Journal
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
Volume 1457, Issue 1, Pages 128-141Publisher
WILEY
DOI: 10.1111/nyas.14201
Keywords
metallacarboranes; therapeutic peptides; thymosin beta 4; conjugates; albumin-binding molecules
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Funding
- National Science Centre, Poland [2015/19/N/NZ7/02726, 2016/23/D/NZ1/02611]
- HIIET PAS
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Metallacarboranes are anionic boron clusters with high affinity to serum albumin, ability to cross biological membranes, and no apparent toxicity in vitro and in vivo. Thus, conjugation with cobalt bis(1,2-dicarbollide), [COSAN](-), ([3,3 '-Co(1,2-C2B9H11)(2)](-)) may improve the properties of therapeutic peptides or proteins at both molecular and systemic levels. Here, we conjugated [COSAN](-) with the therapeutic peptide thymosin beta 4 (T beta 4), which has a pleiotropic activity that results in enhanced healing and regeneration of injured tissues. Using fluorescence quenching of human serum albumin and surface plasmon resonance techniques, we showed that the conjugates have a high affinity to human serum albumin. Using an in vitro wound closure assay, we showed that conjugation with [COSAN](-) enhances the activity of T beta 4 toward fibroblasts (MSU1.1 cell line). These results indicate an application of metallacarboranes in the development of analogs of various therapeutic peptides/proteins with superior pharmacological properties.
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