Switch-Peptides: From Conformational Studies to Alzheimer's Disease
Autor: | Jacques Dubochet, John Lopez, Marc Adrian, Gabriele Tuchscherer, Manfred Mutter, Karine Murat, Lydiane Saucède, Marie-Stephanie Camus, Hilal A. Lashuel, Arunan Chandravarkar, Bhubaneswar Mandal, Richard Mimna, Jeremy Berard, Eric Grouzmann, Sonia Dos Santos |
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Jazyk: | němčina |
Rok vydání: | 2006 |
Předmět: |
Induction of biological function
PYP (Physical process) Amyloid beta Drug design engineering or chemical process) BIOL (Biological study) Disease conformational transitions and Alzheimer's disease) unclassified) designing switch-peptides Conformational transition Protein folding (designing switch-peptides Degenerative diseases Disease (degenerative Rational drug design PROC (Process) (switch-peptides review protein switch peptide conformation transition Alzheimer degenerative disease QD1-999 PEP (Physical biology Chemistry Conformation (protein Rational design General Medicine General Chemistry Alzheimer's disease Proteins Role: BSU (Biological study Folding (chemistry) Switch-peptides Peptide backbone Biochemistry Biophysics biology.protein Protein folding Peptides Protein misfolding |
Zdroj: | CHIMIA, Vol 60, Iss 4 (2006) |
ISSN: | 2673-2424 0009-4293 |
Popis: | Studies on designed peptides that exhibit high tendencies for medium-induced conformational transitions have recently attracted much attention because structural changes are considered as molecular key processes in degenerative diseases. The experimental access to these events has been limited so far mainly due to the intrinsic tendency of the involved polypeptides for self-association and aggregation, e.g. amyloid ? plaque formation, thought to be at the origin of Alzheimer's disease. We have developed a new concept termed 'switch-peptides' which allows the controlled onset of polypeptide folding and misfolding in vitro and in vivo, starting from a soluble, non-toxic precursor molecule. As a major feature, the folding process is initiated by enzyme-triggered N,O-acyl migrations restoring the native peptide backbone in situ. As the folding is set off in the moment of creating the bioactive molecule ('in statu nascendi', ISN), our concept allows for the first time the investigation of the early steps of protein misfolding as relevant in degenerative diseases, opening new perspectives for the rational design of therapeutically relevant compounds. |
Databáze: | OpenAIRE |
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