The sequential triggering (Soff --> Son) of O, N-acyl migrations (AcM) by chemical and enzymatic methods (Ti) in peptides containing structure-disrupting switch-elements, S (switch-peptides), offers a novel tool for studying in statu nascendi the onset and inhibition of polypeptide folding and self-assembly as a key process in degenerative diseases.
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http://dx.doi.org/10.1021/ja052083v | DOI Listing |
Nat Commun
June 2023
Department of Chemistry and Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, USA.
Cryptic sites are short signaling peptides buried within the native extracellular matrix (ECM). Enzymatic cleavage of an ECM protein reveals these hidden peptide sequences, which interact with surface receptors to control cell behavior. Materials that mimic this dynamic interplay between cells and their surroundings via cryptic sites could enable application of this endogenous signaling phenomenon in synthetic ECM hydrogels.
View Article and Find Full Text PDFInt J Cardiol
May 2019
Biomedical Sciences, University of Hull, Cottingham Rd, HU6 7RX Hull, UK. Electronic address:
Background: The inhibitory subunit of cardiac troponin (cTnI) is a gold standard cardiac biomarker and also an essential protein in cardiomyocyte excitation-contraction coupling. The interactions of cTnI with other proteins are fine-tuned by post-translational modification of cTnI. Mutations in cTnI can lead to hypertrophic cardiomyopathy.
View Article and Find Full Text PDFJ Pept Sci
January 2011
Biomolecular Interactions, German Cancer Research Center, Im Neuenheimer Feld, D-69120 Heidelberg, Germany.
In some naturally occurring protein sequences, an abrupt, concerted refolding from β-sheet to helical conformation occurs when the polarity of the surrounding medium drops below a critical level. This switch-like behaviour was first observed on the HIV-1 envelope glycoprotein gp120, where it plays a crucial role in the efficient binding of gp120 to the T-cell receptor CD4. Previous work had shown that an N-terminal amino acid tetrad LPCR and a Trp located 5-20 residues downstream to the tetrad are common motifs in polarity-driven switch peptides.
View Article and Find Full Text PDFOrg Lett
November 2008
Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva, Israel.
A new transformation based on the Staudinger reaction is described, and its application in the design of a novel switch element to control peptide folding is demonstrated. We found that the azide switch is activated rapidly in water to promote acyl transfer using tris(2-carboxyethyl)phosphine hydrochloride (TCEP) via the Staudinger reaction. Our findings expand the repertoire of uses of the Staudinger reaction in chemical biology and the number of available triggers for use in switch peptides.
View Article and Find Full Text PDFChembiochem
September 2008
Institute of Chemical Sciences and Engineering (ISIC), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Several amyloid-forming proteins are characterized by the presence of hydrophobic and highly amyloidogenic core sequences that play critical roles in the initiation and progression of amyloid fibril formation. Therefore targeting these sequences represents a viable strategy for identifying candidate molecules that could interfere with amyloid formation and toxicity of the parent proteins. However, the highly amyloidogenic and insoluble nature of these sequences has hampered efforts to develop high-throughput fibrillization assays.
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