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Covalent Tethering and Residues with Bulky Hydrophobic Side Chains Enable Self‐Assembly of Distinct Amyloid Structures
Author(s) -
Ruiz Jérémy,
Boehringer Régis,
Grogg Marcel,
Raya Jésus,
Schirer Alicia,
Crucifix Corinne,
Hellwig Petra,
Schultz Patrick,
Torbeev Vladimir
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600440
Subject(s) - tethering , covalent bond , side chain , self assembly , chemistry , amyloid (mycology) , stereochemistry , biophysics , combinatorial chemistry , nanotechnology , materials science , organic chemistry , biology , polymer , microbiology and biotechnology , inorganic chemistry
Polymorphism is a common property of amyloid fibers that complicates their detailed structural and functional studies. Here we report experiments illustrating the chemical principles that enable the formation of amyloid polymorphs with distinct stoichiometric composition. Using appropriate covalent tethering we programmed self‐assembly of a model peptide corresponding to the [20–41] fragment of human β2‐microglobulin into fibers with either trimeric or dimeric amyloid cores. Using a set of biophysical and biochemical methods we demonstrated their distinct structural, morphological, and templating properties. Furthermore, we showed that supramolecular approaches in which the peptide is modified with bulky substituents can also be applied to modulate the formation of different fiber polymorphs. Such strategies, when applied to disease‐related peptides and proteins, will greatly help in the evaluation of the biological properties of structurally distinct amyloids.