Dextranol: An inert xeroprotectant

• Published in: PloS one 2019-09, Vol.14 (9), p.e0222006-e0222006
• Main Authors: Jones, Bryan J, Mahajan, Advitiya, Aksan, Alptekin
• Format: Article
• Language: English
• Subjects: Alcohols; Aldehydes; Amadori compounds; Antigens; Backup software; Biological markers; Biological products; Biology and Life Sciences; Biomarkers; Biomedical materials; Blood proteins; Blood Proteins - chemistry; Conjugates; Conjugation; Damage detection; Damage prevention; Desiccants; Desiccation; Dextran; Dextrans; Dextrans - chemistry; Dextrans - pharmacology; Drug Compounding; Enzymes; Freeze drying; High temperature; Immunoassay; Laboratories; Mass spectrometry; Matrix metalloproteinase; Matrix metalloproteinases; Mechanical engineering; Medical research; Metalloproteinase; Molecular weight; Neuropilin; Osteopontin; Oxidation-Reduction; Pharmaceutical sciences; Physical Sciences; Polysaccharides; Preservation, Biological - methods; Prostate cancer; Prostate specific antigen; Protein Stability - drug effects; Proteins; Research and Analysis Methods; Scientific imaging; Serum proteins; Storage; Switching; Temperature
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0222006

Dextranol, a reduced dextran, prevents damage to stored dry protein samples that unmodified dextran would otherwise cause. Desiccation protectants (xeroprotectants) like the polysaccharide dextran are critical for preserving dried protein samples by forming a rigid glass that protects entrapped protein molecules. Stably dried proteins are important for maintaining critical information in clinical samples like blood serum as well as maintaining activity of biologic drug compounds. However, we found that dextran reacts with both dried serum proteins and lyophilized purified proteins during storage, producing high-molecular weight Amadori-product conjugates. These conjugates appeared in a matter of days or weeks when stored at elevated temperatures (37° or 45°C), but also appeared on a timescale of months when stored at room temperature. We synthesized a less reactive dextranol by reducing dextran's anomeric carbon from an aldehyde to an alcohol. Serum samples dried in a dextranol-based matrix protected the serum proteins from forming high-molecular weight conjugates. The levels of four cancer-related serum biomarkers (prostate specific antigen, neuropilin-1, osteopontin, and matrix-metalloproteinase 7) decreased, as measured by immunoassay, when serum samples were stored for one to two weeks in dextran-based matrix. Switching to a dextranol-based xeroprotection matrix slightly reduced the damage to osteopontin and completely stopped any detectable damage during storage in the other three biomarkers when stored for a period of two weeks at 45°C. We also found that switching from dextran to dextranol in a lyophilization formulation eliminates this unwanted reaction, even at elevated temperatures. Dextranol offers a small and easy modification to dextran that significantly improves the molecule's function as a xeroprotectant by eliminating the potential for damaging protein-polysaccharide conjugation.