Spontaneously Cleavable Glycosylated Linker Capable of Extended Release of Its Conjugated Peptide

Reversibly glycosylated conjugates were developed by adding complex-type N-linked oligosaccharides to peptides through self-cleavable linkers with the aim of increasing the solubility and stability of the peptides in plasma. The amino or carboxyl group of the peptide was connected to a glycosylated...

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Veröffentlicht in:Chemical & pharmaceutical bulletin 2019/03/01, Vol.67(3), pp.236-243
Hauptverfasser: Ochiai, Hirofumi, Yoshida, Kenta, Shibutani, Hiroshi, Kanatani, Akio, Nishiuchi, Yuji
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Sprache:eng
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Zusammenfassung:Reversibly glycosylated conjugates were developed by adding complex-type N-linked oligosaccharides to peptides through self-cleavable linkers with the aim of increasing the solubility and stability of the peptides in plasma. The amino or carboxyl group of the peptide was connected to a glycosylated Ascendis or ester/thioester-type linker, respectively. Use of the linkers enabled extended release of the peptides depending on the pH and temperature of the buffer according to a first order reaction, and their cleavage rate was also affected by the structure of the peptide-linker coupling. This tunability will allow optimization towards the intended use of the peptides to be released. Furthermore, because glycosylation is a reliable method of greatly increasing the solubility of a peptide, the presented glycosylated linkers are expected to permit the preparation of antibodies in aqueous buffers even in the case of sparingly soluble antigen peptides.
ISSN:0009-2363
1347-5223
DOI:10.1248/cpb.c18-00626