TY - JOUR
T1 - Improvement of water solubility of mercaptoundecahydrododecaborate (Bsh)-peptides by conjugating with ethylene glycol linker and interaction with cyclodextrin
AU - Kitamatsu, Mizuki
AU - Nakamura-Tachibana, Ayaka
AU - Ishikawa, Yoshimichi
AU - Michiue, Hiroyuki
N1 - Funding Information:
Funding: This research was funded by Takeda Science Foundation.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/1
Y1 - 2021/1
N2 - We previously developed a conjugate consisting of10B cluster BSH and tri-arginine peptide (BSH-3R). This could potentially be used as a boron agent for boron neutron capture therapy; however, it possesses poor water solubility and thus needs to be improved for use as medicine. In this study, we devised several means of improving the water solubility of BSH-3R. As one of them, we used cyclodextrin (CD), which was expected to improve the water solubility resulting from interaction of the BSH-3R with CD. We evaluated the solubility of BSH-3R in aqueous CD solution by using reverse-phase high-performance liquid chromatography. As we expected, the solubility of BSH-3R was increased in a manner dependent on the addition of β-CD and γ-CD in aqueous solution. Furthermore, we synthesized BSH conjugated to oligoarginine having various chain lengths (BSH-nR) and BSH-3R with ethylene glycol linkers introduced between BSH and 3R (BSH-nEg-3R). The water solubility of these BSH peptides was also evaluated and the results showed that the introduction of nEg to BSH-3R markedly improved the water solubility. Furthermore, we found that the water solubility of these peptides can be further improved by also applying CD.
AB - We previously developed a conjugate consisting of10B cluster BSH and tri-arginine peptide (BSH-3R). This could potentially be used as a boron agent for boron neutron capture therapy; however, it possesses poor water solubility and thus needs to be improved for use as medicine. In this study, we devised several means of improving the water solubility of BSH-3R. As one of them, we used cyclodextrin (CD), which was expected to improve the water solubility resulting from interaction of the BSH-3R with CD. We evaluated the solubility of BSH-3R in aqueous CD solution by using reverse-phase high-performance liquid chromatography. As we expected, the solubility of BSH-3R was increased in a manner dependent on the addition of β-CD and γ-CD in aqueous solution. Furthermore, we synthesized BSH conjugated to oligoarginine having various chain lengths (BSH-nR) and BSH-3R with ethylene glycol linkers introduced between BSH and 3R (BSH-nEg-3R). The water solubility of these BSH peptides was also evaluated and the results showed that the introduction of nEg to BSH-3R markedly improved the water solubility. Furthermore, we found that the water solubility of these peptides can be further improved by also applying CD.
KW - BSH
KW - Cell-penetrating peptide
KW - Cyclodextrin
KW - Ethylene glycol
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U2 - 10.3390/pr9010167
DO - 10.3390/pr9010167
M3 - Article
AN - SCOPUS:85099823849
SN - 2227-9717
VL - 9
SP - 1
EP - 11
JO - Processes
JF - Processes
IS - 1
M1 - 167
ER -