Synthesis and characterization of enzymatically biodegradable PEG and peptide-based hydrogels prepared by click chemistry.
Herein we describe the synthesis and rheological characterization of a series of enzymatically sensitive PEG and peptide-based hydrogels by the Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction. The hydrogels were synthesized by a combination of alkyne-functionalized star-shaped PEG molecules (two 4-armed PEGs with M(w) 10 and 20 kDa, respectively, and one 8-armed PEG of 20 kDa) and the protease-sensitive bis-azido peptide, N(alpha)-(azido)-D-alanyl-phenylalanyl-lysyl-(2-azidoethyl)-amide (6) in the presence of CuSO(4) and sodium ascorbate in aqueous solution. The swelling ratio and the storage modulus (G') of the hydrogels could be tailored by several parameters, for example, the initial solid content of the hydrogel, the molecular weight of the PEG derivative, and by the architecture of the PEG molecule (4- versus 8-armed PEG derivative). The peptide sequence, D-Ala-Phe-Lys, was sensitive toward the proteases plasmin and trypsin to render the hydrogels biodegradable.
van Dijk
Maarten
M
Division of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Faculty of Science, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
van Nostrum
Cornelus F
CF
Hennink
Wim E
WE
Rijkers
Dirk T S
DT
Liskamp
Rob M J
RM
D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003300:Copper / Q000737:chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry; D003500:Cyclization; D005341:Fibrinolysin / Q000737:chemistry*; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D006868:Hydrolysis; D015394:Molecular Structure; D008970:Molecular Weight; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D012212:Rheology; D012995:Solubility; D012996:Solutions; D013379:Substrate Specificity; D013499:Surface Properties; D014357:Trypsin / Q000737:chemistry*
D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D010455:Peptides; D012996:Solutions; D011092:Polyethylene Glycols; D003300:Copper; D014357:Trypsin; D005341:Fibrinolysin