title: Rational design of multifunctional hetero-hexameric proteins for hydrogel formation and controlled delivery of bioactive molecules.
abstract: 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.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin, 300071, P. R. China; Key Laboratory of Bioactive Materials, Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin, 300071, P. R. China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: Chunhua
authors.initials: C
authors.lastname: Ren
authors.forename: Dan
authors.initials: D
authors.lastname: Ding
authors.forename: Jiafu
authors.initials: J
authors.lastname: Long
authors.forename: Zhimou
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D002473:Cell Wall / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D008024:Ligands; D013296:Streptococcus pneumoniae / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D003692:Delayed-Action Preparations; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; C421249:TAX1BP3 protein, human; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D000581:Amidohydrolases; C019665:amidase
keywords: controlled drug release; hydrogels; protein-peptide interaction; recombinant protein