| Autor: |
Nagy-Smith K; Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States.; Department of Chemistry and Biochemistry and Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, United States., Beltramo PJ; Department of Chemistry and Biochemistry and Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, United States., Moore E; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, United States., Tycko R; Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, United States., Furst EM; Department of Chemistry and Biochemistry and Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, United States., Schneider JP; Chemical Biology Laboratory, National Cancer Institute, Frederick, Maryland 21702, United States. |
| Abstrakt: |
Hydrogels prepared from self-assembling peptides are promising materials for medical applications, and using both l- and d-peptide isomers in a gel's formulation provides an intuitive way to control the proteolytic degradation of an implanted material. In the course of developing gels for delivery applications, we discovered that a racemic mixture of the mirror-image β-hairpin peptides, named MAX1 and DMAX1, provides a fibrillar hydrogel that is four times more rigid than gels formed by either peptide alone-a puzzling observation. Herein, we use transmission electron microscopy, small angle neutron scattering, solid state NMR, diffusing wave, infrared, and fluorescence spectroscopies, and modeling to determine the molecular basis for the increased mechanical rigidity of the racemic gel. We find that enantiomeric peptides coassemble in an alternating fashion along the fibril long axis, forming an extended heterochiral pleat-like β-sheet, a structure predicted by Pauling and Corey in 1953. Hydrogen bonding between enantiomers within the sheet dictates the placement of hydrophobic valine side chains in the fibrils' dry interior in a manner that allows the formation of nested hydrophobic interactions between enantiomers, interactions not accessible within enantiomerically pure fibrils. Importantly, this unique molecular arrangement of valine side chains maximizes inter-residue contacts within the core of the fibrils resulting in their local stiffening, which in turn, gives rise to the significant increase in bulk mechanical rigidity observed for the racemic hydrogel. |
