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05:48
Controlled Photoredox Ring-Opening Polymerization of O-Carboxyanhydrides Mediated by Ni/Zn Complexes
Published on: November 21, 2017
Degradable conjugates from oxanorbornadiene reagents
Alexander A Kislukhin1, Cody J Higginson, Vu P Hong
1Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Journal of the American Chemical Society
|March 30, 2012
Summary
Oxanorbornadienedicarboxylate (OND) reagents enable controlled drug release from serum albumin carriers. By modifying OND linkages, drug release rates can be tuned from minutes to days for versatile therapeutic applications.
Area of Science:
- Chemical Biology
- Drug Delivery
- Bioconjugation Chemistry
Background:
- Serum albumins are key macromolecular carriers for drug delivery.
- Developing efficient and controllable drug release mechanisms is crucial for therapeutic efficacy.
Purpose of the Study:
- To explore oxanorbornadienedicarboxylate (OND) reagents for binding and releasing drugs from serum albumins.
- To investigate modifications influencing adduct stability and drug release kinetics.
Main Methods:
- Synthesis and characterization of over 30 model OND adducts with thiols and amines.
- Reaction kinetics studies involving bovine serum albumin (BSA) cysteine and amine residues.
- Assessment of OND-adduct stability under various conditions (pH, temperature).
- Evaluation of drug release profiles using fluorescent cargo.
Main Results:
- OND reagents efficiently label BSA cysteine residues within minutes at mid-micromolar concentrations.
- High selectivity (>1000-fold) for thiol over amine labeling was observed in model systems, but protein amine labeling is also practical.
- OND-amine adducts exhibit up to 15-fold greater stability than OND-thiol adducts and are sensitive to acid-catalyzed release.
- Drug release half-lives from BSA ranged from 40 minutes to 7 days, tunable by OND linkage modification.
Conclusions:
- OND reagents offer a versatile platform for developing tunable drug release systems from protein carriers.
- The ability to control release rates by modifying OND linkages provides a valuable tool for drug delivery applications.
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