The use of benign stimuli to control the binding and release of labile biologics for their isolation from complex feedstocks is a key goal of modern biopharmaceutical technology. This study introduces cyclic azobenzene‐peptide (CAP) ligands for the rapid and discrete photo‐responsive capture and release of blood coagulation factor VIII (FVIII). A predictive method—based on amino acid sequence and molecular architecture of CAPs—is developed to correlate the conformation of
This content will become publicly available on December 28, 2024
Sepsis, whole‐body inflammation caused by the contamination of blood by bacteria and endotoxins, affects millions of patients annually with high mortality rates. A recent promising approach to treat sepsis involves the removal of bacteria and endotoxins using extracorporeal blood‐cleansing devices. However, poor specificity, slow recognition of pathogens, and high costs remain the main limitations. Here, the melanin, a biologically derived pigment, is reported for the rapid binding of bacteria and endotoxins from the contaminated blood . This novel approach utilizes the specific binding between Zn2+‐loaded melanin and bacteria/endotoxins with minimal nonspecific interactions with human blood components. Melanin contains various chemical functional groups that allow reversible chelation of metallic ions such as Zn2+via redox reactions. Zn2+enables rapid and specific binding with bacteria/endotoxins due to the strong electrostatic interactions between Zn2+and phosphate ions. The presence of various zinc‐binding proteins on the bacterial cell membrane further enhances the binding. The well‐known biocompatibility and low cost make melanin an ideal material to interface with human blood. Zn2+‐charged melanin can remove 90% of
- Award ID(s):
- 1757371
- NSF-PAR ID:
- 10486646
- Publisher / Repository:
- Wiley
- Date Published:
- Journal Name:
- Advanced Materials Interfaces
- ISSN:
- 2196-7350
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract cis /trans ‐CAP photo‐isomers to FVIII binding and release. Combined in silico ‐ in vitro analysis of FVIII:peptide interactions guide the design of a rational approach to optimize isomerization kinetics and biorecognition of CAPs. A photoaffinity adsorbent, prepared by conjugating selected CAP G‐cycloAZOB[Lys‐YYKHLYN‐Lys]‐G on translucent chromatographic beads, features high binding capacity (>6 mg of FVIII per mL of resin) and rapid photo‐isomerization kinetics (τ < 30 s) when exposed to 420–450 nm light at the intensity of 0.1 W cm−2. The adsorbent purifies FVIII from a recombinant harvest using a single mobile phase, affording high product yield (>90%), purity (>95%), and blood clotting activity. The CAPs introduced in this report demonstrate a novel route integrating gentle operational conditions in a rapid and efficient bioprocess for the purification of life‐saving biotherapeutics. -
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