Molecular modeling and correlation of PFI1625c-peptide models of bioactive peptides with antimalarial properties

Lhouvum, Kimjolly; Bhuyar, Kshitij Shekhar; Trivedi, Vishal

doi:10.1007/s00044-014-1232-5

“…6). However, presumably ABS parasites still have a comparably high need for MPP activity to facilitate mitochondrial function outside of respiration, as exemplified by putative MPPβ inhibitors showing promise as antimalarials 79,80 .…”

Section: Discussionmentioning

confidence: 99%

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Evers

¹

,

Cabrera‐Orefice

²

,

Elurbe

³

et al. 2021

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Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

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“…6). However, presumably ABS parasites still have a comparably high need for MPP activity to facilitate mitochondrial function outside of respiration, as exemplified by putative MPPβ inhibitors showing promise as antimalarials (77,78). This would necessitate synthesis of the whole complex, which is much less efficient and more challenging from a regulatory standpoint than generating the heterodimer observed in the mitochondria of its host.…”

Section: Discussionmentioning

confidence: 99%

Composition and stage dynamics of mitochondrial complexes inPlasmodium falciparum

Evers¹,

Cabrera‐Orefice

²

,

Elurbe

³

et al. 2020

Preprint

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Our current understanding of mitochondrial functioning is largely restricted to traditional model organisms, which only represent a fraction of eukaryotic diversity. The unusual mitochondrion of malaria parasites is a validated drug target but remains poorly understood. Here, we apply complexome profiling to map the inventory of protein complexes across the pathogenic asexual blood stages and the transmissible gametocyte stages of Plasmodium falciparum. We identify remarkably divergent composition and clade-specific additions of all respiratory chain complexes. Furthermore, we show that respiratory chain complex components and linked metabolic pathways are up to 40-fold more prevalent in gametocytes, while glycolytic enzymes are substantially reduced. Underlining this functional switch, we find that cristae are exclusively present in gametocytes. Leveraging these divergent properties and stage dynamics for drug development presents an attractive opportunity to discover novel classes of antimalarials and increase our repertoire of gametocytocidal drugs.

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“…Peptides released from food protein by enzymatic hydrolysis had been reported to manifest various bioactivities such as immune regulation (Gauthier, Pouliot, & Saint-Sauveur, 2006), antiinflammatory (Mukhopadhya et al, 2014), antihypertensive (Hernández-Ledesma, del Mar Contreras, & Recio, 2011), antioxidant (Kleekayai et al, 2015), and antimalarial (Lhouvum, Bhuyar, & Trivedi, 2015). Amongst them, peptides with immunomodulatory ability had been focused on by more and more researchers.…”

Section: Introductionmentioning

confidence: 99%

Immunomodulatory activity of small molecular (≤3 kDa)Coixglutelin enzymatic hydrolysate

L

¹

,

Li

²

,

Ji

³

et al. 2016

CyTA - Journal of Food

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2017)Immunomodulatory activity of small molecular (≤3 kDa) Coix glutelin enzymatic hydrolysate, CyTA -Journal of Food, 15:1, 41-48, ABSTRACT In this study, small molecular (≤3 kDa) Coix glutelin hydrolysate (CGH) was obtained by the method of enzymatic hydrolysis and then immunomodulatory activity was evaluated in vitro and in vivo. Stimulation index of mice splenocytes was increased in a dose-dependent manner after treated with 3.125-25 μg/mL CGH. Acid phosphatase in mice peritoneal macrophages was significantly improved after stimulated with CGH at some concentration. The CGH stimulated the secretion of NO from Raw264.7 in a concentration-dependent manner and also significantly inhibited lipopolysaccharideinduced cell excessive activation at some extent. After successive administration of CGH for 21 days, the spleen index of ICR was significantly increased to 3.73 mg/g for the group administrated 800 mg/kg CGH. Malondialdehyde (MDA) assay displayed that 200 mg/kg CGH increased mice serum MDA concentration, while the variation was obsolete in the other CGH groups. All results demonstrated that CGH took essential effects on immunomodulatory activities.Actividad inmunomoduladora de hidrolisato glutelina encimático de moléculas pequeñas de Coix (≤ 3 kDa) RESUMEN En este estudio, se obtuvo hidrolisato glutelina de Coix (CGH) de molécula pequeña (≤ 3 kDa) mediante el método de hidrólisis enzimática y después se evaluó la actividad sinmunomoduladora in vitro y in vivo. El índice de estimulación (SI) de los esplenocitos de ratón aumentó de forma dependiente a la dosis después ser tratados con 3,125-25 μg/mL de CGH. La fosfatasa ácida (ACP) en los macrófagos peritoneales de ratón mejoró significativamente después de que se estimulara con CGH en algunas concentraciones. El CGH estimuló la secreción de NO a partir de Raw264.7 de forma dependiente de la concentración e inhibió de forma significativa la activación excesiva de células inducidas con LPS en cierta medida. Después de una administración sucesiva de CGH durante 21 días, el índice esplénico de ICR aumentó significativamente a 3,73 mg/g para el grupo al cual se había administrado 800 mg/kg de CGH. El ensayo de malondialdehído (MDA) mostró que los 200 mg/kg de CGH hicieron aumentar la concentración de MDA del suero de ratón, mientras que la variación fue obsoleta en los otros grupos de CGH. Todos los resultados demostraron que CGH obtuvo efectos esenciales en las actividades inmunomoduladoras. ARTICLE HISTORY

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Molecular modeling and correlation of PFI1625c-peptide models of bioactive peptides with antimalarial properties

Cited by 7 publications

References 39 publications

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum

Composition and stage dynamics of mitochondrial complexes inPlasmodium falciparum

Immunomodulatory activity of small molecular (≤3 kDa)Coixglutelin enzymatic hydrolysate

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