Synthesis and Biological Activity of Thymosin β4-Anionic Boron Cluster Conjugates

Area of Science:

• Inorganic Chemistry
• Bioconjugation Chemistry
• Medicinal Chemistry

Background:

• Anionic boron clusters are synthetic inorganic compounds with potential in modifying therapeutic peptides.
• Improving peptide biological activity and pharmacokinetics, such as serum albumin complexation, is a key challenge.
• The conjugation of anionic boron clusters with peptides is not well understood.

Purpose of the Study:

• To develop a method for selectively conjugating anionic boron clusters to peptides.
• To investigate the stability and biological activity of the resulting peptide-cluster conjugates.
• To explore the potential of these conjugates in therapeutic applications.

Main Methods:

• A solid-state, thermal reaction was employed for conjugation.
• Carboxylic groups of thymosin β4 (Tβ4) were selectively modified with cyclic oxonium derivatives of dodecaborate anion ([B12H12]2-) and cobalt bis(1,2-dicarbollide) ([COSAN]-).
• Ester bond formation and hydrolysis rates were analyzed to determine conjugate stability.

Main Results:

• Selective conjugation of Tβ4 with [B12H12]2- and [COSAN]- via ester bonds was achieved.
• The modification retained the negative charge at the conjugation site.
• Conjugates exhibited significantly different stabilities (half-lives from 3-836 h for Tβ4-[B12H12]2- and 9-1329 h for Tβ4-[COSAN]-).
• The prosurvival activity of Tβ4 toward cardiomyocytes was retained or improved.

Conclusions:

• A novel solid-state reaction enables selective conjugation of anionic boron clusters to Tβ4.
• The resulting Tβ4-boron cluster conjugates demonstrate tunable stability.
• These conjugates maintain or enhance the therapeutic prosurvival activity of Tβ4, suggesting potential for drug development.