title: Enzymatic modification of self-assembled peptide structures with tissue transglutaminase.
abstract: A de novo peptide that self-assembles into fibrillar structures and serves as a substrate for the cross-linking enzyme tissue transglutaminase was developed (Ac-QQKFQFQFEQQ-Am). Congo red staining, circular dichroism, and FTIR spectroscopy showed that this 11-amino acid peptide produced predominantly beta-sheet structures. TEM with negative staining and quick-freeze deep etch (QFDE) TEM showed that the peptide structures were composed of a highly entangled fibrillar network. These beta-sheet fibrillar nanostructures were then covalently coupled to pendant amine-containing biomolecules via tissue transglutaminase. MALDI-TOF mass spectrometry and HPLC were utilized to monitor the extent of the transglutaminase modification of the peptide, showing that as many as five glutamines in the peptide were reactive via transglutaminase for covalent conjugation. This strategy, based on the post-assembly modification of a self-assembling peptide, has potential applications for tailoring supramolecular structures for drug delivery, tissue engineering, or other biomedical applications.
authors.affiliation: Northwestern University, Department of Biomedical Engineering, 2145 Sheridan Road, Room E310, Evanston, Illinois 60208, USA.
authors.forename: Joel H
authors.initials: JH
authors.lastname: Collier
authors.forename: Phillip B
authors.initials: PB
authors.lastname: Messersmith
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000682:Amyloid / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D013058:Mass Spectrometry; D008854:Microscopy, Electron / Q000379:methods; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors; D011503:Transglutaminases / Q000737:chemistry / Q000378:metabolism*; D014867:Water / Q000737:chemistry
chemical_list: D000682:Amyloid; D010455:Peptides; D014867:Water; D011503:Transglutaminases