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Rational Design of Multifunctional Hetero‐Hexameric Proteins for Hydrogel Formation and Controlled Delivery of Bioactive Molecules
Author(s) -
Zhang Xiaoli,
Zhou Hao,
Xie Ying,
Ren Chunhua,
Ding Dan,
Long Jiafu,
Yang Zhimou
Publication year - 2014
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201300660
Subject(s) - self healing hydrogels , moiety , nanofiber , docking (animal) , drug delivery , rational design , biophysics , chemistry , molecule , nanotechnology , materials science , combinatorial chemistry , stereochemistry , biology , polymer chemistry , organic chemistry , medicine , nursing
A hetero‐hexameric protein system is developed in this study, which not only functions as cross‐linkers for hydrogel formation but also offers docking sites for controlled delivery of bioactive molecules. First, a hexameric protein with two, four, and six tax‐interacting protein‐1 (TIP‐1), respectively (named as 2T, 4T, and 6T), is designed and obtained. As the hexapeptide ligand (WRESAI) can specifically bind to TIP‐1 with high affinity, the hexameric proteins of 2T, 4T, and 6T can be used to crosslink the self‐assembling nanofibers of Nap‐GFFYGGGWRESAI, leading to formation of injectable biohybrid hydrogels with tunable mechanical properties. Furthermore, a hetero‐hexameric protein containing four TIP‐1 and two C‐terminal moiety of the pneumococcal cell‐wall amidase LytA (C‐LytA) proteins is designed and engineered (named as 4T2C). The 4T2C proteins can not only serve as cross‐linkers for hydrogel formation but also provide docking sites for loading and controlled release of model drug Rhoda‐GGK′. This study opens up new opportunities for further development of multifunctional hetero‐ recombinant protein‐based hydrogels for biological applications.