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Updated: Aug 22, 2025

Activation and Conjugation of Soluble Polysaccharides using 1-Cyano-4-Dimethylaminopyridine Tetrafluoroborate CDAP
Published on: June 14, 2021
A Poly-ADP-Ribose Polymer-GCSF Conjugate
Qinqin Cheng1, Xiao-Nan Zhang1, Lei Zhang1
1Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90089, United States.
Abstract:
Poly-ADP-ribose (PAR) is a naturally occurring form of polymers synthesized through enzymatic reactions catalyzed by poly(ADP-ribose) polymerases (PARPs). It is known for regulating various important cellular signaling pathways and processes. As a water soluble and biocompatible type of polymer, PAR may hold promise for safe and efficient delivery of therapeutics. To explore the therapeutic potential of PAR polymers, we herein generate PAR polymers conjugated with human granulocyte colony-stimulating factor (GCSF) protein by harnessing human PARP1-catalyzed auto-poly-ADP-ribosylation and a clickable analogue of nicotinamide adenine dinucleotide (NAD+). The resulting PAR polymer-based conjugate with multivalent GCSF ligands exhibits a potent cell proliferative activity. Notably, mice treated with a single dose of the PAR polymer-GCSF conjugate show sustained high levels of neutrophil in blood for 11 days, demonstrating excellent in vivo efficacy. Functionalized PAR polymers may provide new scaffolds for conjugating with therapeutic proteins or peptides toward improved pharmacological activities.
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