Self-assembling amphipathic alpha-helical peptides induce the formation of active protein aggregates in vivo

2013 ◽  
Vol 166 ◽  
pp. 243 ◽  
Author(s):  
Zhanglin Lin ◽  
Bihong Zhou ◽  
Wei Wu ◽  
Lei Xing ◽  
Qing Zhao
Keyword(s):  
Protein Aggregates ◽  
Active Protein ◽  
Helical Peptides ◽  
Self Assembling ◽  
Alpha Helical Peptides

Assembly of active protein aggregates in vivo induced by terminally attached amphipathic octadecapeptide

2010 ◽  
Vol 150 ◽  
pp. 86-86 ◽  
Author(s):  
Z. Lin ◽  
W. Wu ◽  
L. Xing ◽  
Z. Cai ◽  
B. Chen
Keyword(s):  
Protein Aggregates ◽  
Active Protein

Half-Life of Platelet Factor 4 (PF-4) in Plasma and Platelets from Macaca Mulatta

1977 ◽  
Vol 37 (01) ◽  
pp. 073-080 ◽  
Author(s):  
Knut Gjesdal ◽  
Duncan S. Pepper
Keyword(s):  
Macaca Mulatta ◽  
Half Life ◽  
Human Platelet ◽  
Gel Filtration ◽  
Platelet Factor 4 ◽  
Active Protein ◽  
Platelet Factor ◽  
Membrane Bound

SummaryHuman platelet factor 4 (PF-4) showed a reaction of complete identity with PF-4 from Macaca mulatta when tested against rabbit anti-human-PF-4. Such immunoglobulin was used for quantitative precipitation of in vivo labelled PF-4 in monkey serum. The results suggest that the active protein had an intra-platelet half-life of about 21 hours. In vitro 125I-labelled human PF-4 was injected intravenously into two monkeys and isolated by immuno-precipita-tion from platelet-poor plasma and from platelets disrupted after gel-filtration. Plasma PF-4 was found to have a half-life of 7 to 11 hours. Some of the labelled PF-4 was associated with platelets and this fraction had a rapid initial disappearance rate and a subsequent half-life close to that of plasma PF-4. The results are compatible with the hypothesis that granular PF-4 belongs to a separate compartment, whereas membrane-bound PF-4 and plasma PF-4 may interchange.

scholarly journals Frequency- and Afterload-Dependent Cardiac Modulation In Vivo by Troponin I With Constitutively Active Protein Kinase A Phosphorylation Sites

2004 ◽  
Vol 94 (4) ◽  
pp. 496-504 ◽  
Author(s):  
Eiki Takimoto ◽  
David G. Soergel ◽  
Paul M.L. Janssen ◽  
Linda B. Stull ◽  
David A. Kass ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Troponin I ◽  
Phosphorylation Sites ◽  
Active Protein ◽  
Cardiac Modulation ◽  
Kinase A ◽  
Constitutively Active

scholarly journals Newly Developed Self-Assembling Antioxidants as Potential Therapeutics for the Cancers

2021 ◽  
Vol 11 (2) ◽  
pp. 92 ◽  
Author(s):  
Babita Shashni ◽  
Yukio Nagasaki
Keyword(s):  
Cancer Survival ◽  
Self Assembling ◽  
Therapeutic Regime ◽  
Cancer Models ◽  
Secondary Messengers ◽  
Potential Therapeutics ◽  
Target Effects ◽  
Tempo Radical

Elevated reactive oxygen species (ROS) have been implicated as significant for cancer survival by functioning as oncogene activators and secondary messengers. Hence, the attenuation of ROS-signaling pathways in cancer by antioxidants seems a suitable therapeutic regime for targeting cancers. Low molecular weight (LMW) antioxidants such as 2,2,6,6-tetramethylpyperidine-1-oxyl (TEMPO), although they are catalytically effective in vitro, exerts off-target effects in vivo due to their size, thus, limiting their clinical use. Here, we discuss the superior impacts of our TEMPO radical-conjugated self-assembling antioxidant nanoparticle (RNP) compared to the LMW counterpart in terms of pharmacokinetics, therapeutic effect, and adverse effects in various cancer models.

scholarly journals A biomimetic platelet based on assembling peptides initiates artificial coagulation

2020 ◽  
Vol 6 (22) ◽  
pp. eaaz4107
Author(s):  
Pei-Pei Yang ◽  
Kuo Zhang ◽  
Ping-Ping He ◽  
Yu Fan ◽  
Xuejiao J. Gao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Binding Sites ◽  
Therapeutic Strategy ◽  
Critical Role ◽  
The Self ◽  
Membrane Glycoprotein ◽  
Tumor Site ◽  
Self Assembling ◽  
Receptor Interactions

Platelets play a critical role in the regulation of coagulation, one of the essential processes in life, attracting great attention. However, mimicking platelets for in vivo artificial coagulation is still a great challenge due to the complexity of the process. Here, we design platelet-like nanoparticles (pNPs) based on self-assembled peptides that initiate coagulation and form clots in blood vessels. The pNPs first bind specifically to a membrane glycoprotein (i.e., CD105) overexpressed on angiogenetic endothelial cells in the tumor site and simultaneously transform into activated platelet-like nanofibers (apNFs) through ligand-receptor interactions. Next, the apNFs expose more binding sites and recruit and activate additional pNPs, forming artificial clots in both phantom and animal models. The pNPs are proven to be safe in mice without systemic coagulation. The self-assembling peptides mimic platelets and achieve artificial coagulation in vivo, thus providing a promising therapeutic strategy for tumors.

scholarly journals De novo design of self-assembling helical protein filaments

Science ◽  
2018 ◽  
Vol 362 (6415) ◽  
pp. 705-709 ◽  
Author(s):  
Hao Shen ◽  
Jorge A. Fallas ◽  
Eric Lynch ◽  
William Sheffler ◽  
Bradley Parry ◽  
...  
Keyword(s):  
De Novo ◽  
Computational Design ◽  
Building Blocks ◽  
Repeat Units ◽  
Self Assembling ◽  
Wide Range ◽  
Helical Protein ◽  
Monomeric Proteins

We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. Cryo–electron microscopy structures of six designs are close to the computational design models. The filament building blocks are idealized repeat proteins, and thus the diameter of the filaments can be systematically tuned by varying the number of repeat units. The assembly and disassembly of the filaments can be controlled by engineered anchor and capping units built from monomers lacking one of the interaction surfaces. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.

scholarly journals PrP P102L and Nearby Lysine Mutations Promote Spontaneous In Vitro Formation of Transmissible Prions

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Allison Kraus ◽  
Gregory J. Raymond ◽  
Brent Race ◽  
Katrina J. Campbell ◽  
Andrew G. Hughson ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Transmissible Spongiform Encephalopathy ◽  
Clinical Signs ◽  
Protein Aggregates ◽  
Structural Features ◽  
Spongiform Encephalopathy ◽  
Specific Sequence

ABSTRACT Accumulation of fibrillar protein aggregates is a hallmark of many diseases. While numerous proteins form fibrils by prion-like seeded polymerization in vitro, only some are transmissible and pathogenic in vivo. To probe the structural features that confer transmissibility to prion protein (PrP) fibrils, we have analyzed synthetic PrP amyloids with or without the human prion disease-associated P102L mutation. The formation of infectious prions from PrP molecules in vitro has required cofactors and/or unphysiological denaturing conditions. Here, we demonstrate that, under physiologically compatible conditions without cofactors, the P102L mutation in recombinant hamster PrP promoted prion formation when seeded by minute amounts of scrapie prions in vitro. Surprisingly, combination of the P102L mutation with charge-neutralizing substitutions of four nearby lysines promoted spontaneous prion formation. When inoculated into hamsters, both of these types of synthetic prions initiated substantial accumulation of prion seeding activity and protease-resistant PrP without transmissible spongiform encephalopathy (TSE) clinical signs or notable glial activation. Our evidence suggests that PrP's centrally located proline and lysine residues act as conformational switches in the in vitro formation of transmissible PrP amyloids. IMPORTANCE Many diseases involve the damaging accumulation of specific misfolded proteins in thread-like aggregates. These threads (fibrils) are capable of growing on the ends by seeding the refolding and incorporation of the normal form of the given protein. In many cases such aggregates can be infectious and propagate like prions when transmitted from one individual host to another. Some transmitted aggregates can cause fatal disease, as with human iatrogenic prion diseases, while other aggregates appear to be relatively innocuous. The factors that distinguish infectious and pathogenic protein aggregates from more innocuous ones are poorly understood. Here we have compared the combined effects of prion seeding and mutations of prion protein (PrP) on the structure and transmission properties of synthetic PrP aggregates. Our results highlight the influence of specific sequence features in the normally unstructured region of PrP that influence the infectious and neuropathogenic properties of PrP-derived aggregates.

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