Circular dichroism and electron microscopy studies in vitro of 33‐mer gliadin peptide revealed secondary structure transition and supramolecular organization

Herrera, María Georgina; Zamarreño, Fernando; Costabel, Marcelo Daniel; Ritacco, Hernán; Hütten, Andreas; Sewald, Norbert; Dodero, Verónica Isabel

doi:10.1002/bip.22288

Cited by 35 publications

(65 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peptides may enter the cell by endocytosis, with their entrance into the cells requiring 37 °C temperature and Ca 2+ in the media [84]. It has been shown that these peptides possess structural configuration characterized by a left-handed polyproline II helical conformation that is preferred by MHC class II ligands [85]. …”

Section: Gluten Intolerance Pathogenesismentioning

confidence: 99%

Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

2016

View full text Add to dashboard Cite

Theterm gluten intolerance may refer to three types of human disorders: autoimmune celiac disease (CD), allergy to wheat and non-celiac gluten sensitivity (NCGS). Gluten is a mixture of prolamin proteins present mostly in wheat, but also in barley, rye and oat. Gluten can be subdivided into three major groups: S-rich, S-poor and high molecular weight proteins. Prolamins within the groups possess similar structures and properties. All gluten proteins are evolutionarily connected and share the same ancestral origin. Gluten proteins are highly resistant to hydrolysis mediated by proteases of the human gastrointestinal tract. It results in emergence of pathogenic peptides, which cause CD and allergy in genetically predisposed people. There is a hierarchy of peptide toxicity and peptide recognition by T cells. Nowadays, there are several ways to detoxify gluten peptides: the most common is gluten-free diet (GFD), which has proved its effectiveness; prevention programs, enzymatic therapy, correction of gluten pathogenicity pathways and genetically modified grains with reduced immunotoxicity. A deep understanding of gluten intolerance underlying mechanisms and detailed knowledge of gluten properties may lead to the emergence of novel effective approaches for treatment of gluten-related disorders.

show abstract

Section: Gluten Intolerance Pathogenesismentioning

confidence: 99%

Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

2016

View full text Add to dashboard Cite

show abstract

“…Electron microscopy observations show that the 33‐mer can oligomerize to form nanospheres, fibrils, and fibers that coexist together at 613 μ m . Molecular dynamics simulation and partial charge distribution calculations have revealed that the 33‐mer peptide is a nonionic amphiphile with the capability to form, at least, a stable dimer …”

Section: The Supramolecular Behavior Of 33‐mer Gliadin Peptide: a Newmentioning

confidence: 99%

“… Spontaneous oligomerization of 33‐mer depends on peptide concentration. On increasing the peptide concentration, spherical‐like oligomers undergo a conformational transition towards sheet‐like structures with a parallel β structure …”

Section: The Supramolecular Behavior Of 33‐mer Gliadin Peptide: a Newmentioning

confidence: 99%

See 1 more Smart Citation

Translational Chemistry Meets Gluten‐Related Disorders

2018

View full text Add to dashboard Cite

Gluten‐related disorders are a complex group of diseases that involve the activation of the immune system triggered by the ingestion of gluten. Among these, celiac disease, with a prevalence of 1 %, is the most investigated, but recently, a new pathology, named nonceliac gluten sensitivity, was reported with a general prevalence of 7 %. Finally, there other less‐prevalent gluten‐related diseases such as wheat allergy, gluten ataxia, and dermatitis herpetiformis (with an overall prevalence of less than 0.1 %). As mentioned, the common molecular trigger is gluten, a complex mixture of storage proteins present in wheat, barley, and a variety of oats that are not fully degraded by humans. The most‐studied protein related to disease is gliadin, present in wheat, which possesses in its sequence many pathological fragments. Despite a lot of effort to treat these disorders, the only effective method is a long‐life gluten‐free diet. This Review summarizes the actual knowledge of gluten‐related disorders from a translational chemistry point of view. We discuss what is currently known from the literature about the interaction of gluten with the gut and the critical host responses it evokes and, finally, connect them to our current and novel molecular understanding of the supramolecular organization of gliadin and the 33‐mer gliadin peptide fragment under physiological conditions.

show abstract

“…Moreover, time-dependent CD experiments confirmed the slow transition from unordered to ordered oligomers in the first 3h (Figure 3C), as evidentb yt he slow increaseo ft he minimaa tl % 215 nm and the maxima at l = 195 nm until 7h.A ni sodichroic point was observed at l = 208 nm, which suggesteda two-state transitionf rom randomc oil to b-sheet conformation ( Figure 3C). [36] CD deconvolution with the algorithm BeSt-Sel [37,38] revealed an increase in the amount of b sheets within 1h ( Figures 3D and S3). The ratio between b-sheet structure and unordered conformation increased by 84 %f or 5h.T he antiparallel b-sheet structure, formed in the early oligomerization phase, is the major component that tends to increase during the first hour.S uccessively,t he decrease in the antiparallel component is compensated for by an increasei nt he parallel one ( Figure 3D).…”

mentioning

confidence: 99%

Real‐Time BODIPY‐Binding Assay To Screen Inhibitors of the Early Oligomerization Process of Aβ1–42 Peptide

et al. 2020

Self Cite

View full text Add to dashboard Cite

Misfolding and aggregation of amyloid b1-42 peptide( A b1-42) play ac entral role in the pathogenesis of Alzheimer's disease (AD). Ta rgeting the highly cytotoxic oligomeric species formed during the early stages of the aggregation process represents ap romising therapeutic strategy to reduce the toxicity associated with Ab1-42. Currently,t he thioflavin T( ThT) assay is the only established spectrofluorometric methodt os creen aggregation inhibitors. The successo ft he ThT assay is that it can detect Ab1-42 aggregates with high b-sheet content,s uch as protofibrils or fibrils, which appear in the late aggregation steps. Unfortunately,b yu sing the ThT assay,t he detection of inhibitors of early soluble oligomers that present al ow b-sheet character is challenging. Herein, an ew,f acile, and robust boron-dipyrromethene( BODIPY) real-time assay suitable for 96-well plate format, which allows screening of compounds as selectivei nhibitors of the formation of Ab1-42 oligomers, is reported.T hese inhibitors decrease the cellular toxicityo fA b1-42, although they fail in the ThT assay.T he findings have been confirmed and validated by structural analysis and cell viability assays under comparable experimental conditions. It is demonstrated that the BODIPY assay is ac onvenient methodt o screen and discover new candidate compoundst hat slow down or stop the pathological earlyo ligomerization process and are active in the cellular assay.T herefore, it is as uitable complementary screening method of the current ThT assay.Alzheimer's disease (AD) is ad evastating neurodegenerative disease that leads to progressive cognitive decline, functional impairment, and loss of independence. [1] The number of people worldwide suffering from AD is expected to reach 75 million by 2030, [2] butn oc ausative treatment exists for AD.The search for small molecules that inhibitt he aggregation of the 42-residue amyloid b protein fragment (Ab1-42; Figure 1A) is still ongoing to find at herapy for AD. Ab1-42 spontaneously self-associates into soluble oligomers and insolublea ggregates, such as protofibrilsa nd fibrils with high b-sheetc ontent.I th as been recognized that small and soluble Ab1-42 oligomers are particularly cytotoxic. [3][4][5][6][7] Thus, therapeutics trategies that intervene in the early oligomerization process, rather than in the later fibril formation step, have recently attracted attention. [8] However,d espite its therapeutic significance,t he screening of potentiali nhibitors of the early oligomerization process is still challenging. The thioflavin T( ThT) fluorescencea ssayi su sed routinelytodetermine the influence of compounds on amyloid aggregation kinetics. [9,10] However,T hT only exhibits as ubstantial fluorescencei ncreaseu pon binding to b-sheet-rich amyloid protofilaments and fibrils, but has low sensitivity to soluble early-stage oligomers. [11][12][13][14] Molecules that do not show any apparenti nhibition of amyloid aggregation,a ccording to the ThT assay,a re usually not considered for any subsequentt est...

show abstract

Circular dichroism and electron microscopy studies in vitro of 33‐mer gliadin peptide revealed secondary structure transition and supramolecular organization

Cited by 35 publications

References 70 publications

Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

Translational Chemistry Meets Gluten‐Related Disorders

Real‐Time BODIPY‐Binding Assay To Screen Inhibitors of the Early Oligomerization Process of Aβ1–42 Peptide

Contact Info

Product

Resources

About