scholarly journals Correction: S. mansoni SmKI-1 Kunitz-domain: Leucine point mutation at P1 site generates enhanced neutrophil elastase inhibitory activity

2021 ◽  
Vol 15 (4) ◽  
pp. e0009349
Author(s):  
Keyword(s):  
Point Mutation ◽  
Inhibitory Activity ◽  
Neutrophil Elastase ◽  
Kunitz Domain

scholarly journals S. mansoni SmKI-1 Kunitz-domain: Leucine point mutation at P1 site generates enhanced neutrophil elastase inhibitory activity

2021 ◽  
Vol 15 (1) ◽  
pp. e0009007
Author(s):  
Fábio Mambelli ◽  
Bruno P. O. Santos ◽  
Suellen B. Morais ◽  
Enrico G. T. Gimenez ◽  
Duana C. dos S. Astoni ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Neutrophil Elastase ◽  
Point Mutations ◽  
Point Of View ◽  
Mutant Proteins ◽  
Inflammatory Parameters ◽  
C Terminus ◽  
Kunitz Domain

The Schistosoma mansoni SmKI-1 protein is composed of two domains: a Kunitz-type serine protease inhibitor motif (KD) and a C-terminus domain with no similarity outside the genera. Our previous work has demonstrated that KD plays an essential role in neutrophil elastase (NE) binding blockage, in neutrophil influx and as a potential anti-inflammatory molecule. In order to enhance NE blocking capacity, we analyzed the KD sequence from a structure-function point of view and designed specific point mutations in order to enhance NE affinity. We substituted the P1 site residue at the reactive site for a leucine (termed RL-KD), given its central role for KD’s inhibition to NE. We have also substituted a glutamic acid that strongly interacts with the P1 residue for an alanine, to help KD to be buried on NE S1 site (termed EA-KD). KD and the mutant proteins were evaluated in silico by molecular docking to human NE, expressed in Escherichia coli and tested towards its NE inhibitory activity. Both mutated proteins presented enhanced NE inhibitory activity in vitro and RL-KD presented the best performance. We further tested RL-KD in vivo in an experimental model of monosodium urate (MSU)-induced acute arthritis. RL-KD showed reduced numbers of total cells and neutrophils in the mouse knee cavity when compared to KD. Nevertheless, both RL-KD and KD reduced mice hypernociception in a similar fashion. In summary, our results demonstrated that both mutated proteins showed enhanced NE inhibitory activity in vitro. However, RL-KD had a prominent effect in diminishing inflammatory parameters in vivo.

The constituent, anti-inflammation, and human neutrophil elastase inhibitory activity of Gnaphalium affine

2016 ◽  
Vol 27 ◽  
pp. 674-684 ◽  
Author(s):  
Hyung Won Ryu ◽  
Ki Ohk Kim ◽  
Heung Joo Yuk ◽  
Ok-Kyoung Kwon ◽  
Jung Hee Kim ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Human Neutrophil Elastase ◽  
Anti Inflammation

scholarly journals Effects of structure on inhibitory activity in a series of mechanism-based inhibitors of human neutrophil elastase

2010 ◽  
Vol 18 (18) ◽  
pp. 6646-6650 ◽  
Author(s):  
Dengfeng Dou ◽  
Guijia He ◽  
Rongze Kuang ◽  
Qingfong Fu ◽  
Radhika Venkataraman ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Neutrophil Elastase ◽  
Human Neutrophil ◽  
Human Neutrophil Elastase

Inhibitory effects of bioaccessible anthocyanins and procyanidins from apple, red grape, cinnamon on α-amylase, α-glucosidase and lipase

2020 ◽  
pp. 1-9
Author(s):  
Pınar Ercan ◽  
Sedef Nehir El
Keyword(s):  
Inhibitory Activity ◽  
Digestive Enzymes ◽  
Positive Control ◽  
Anthocyanin Content ◽  
Inhibitory Effects ◽  
Total Anthocyanin ◽  
Total Anthocyanin Content ◽  
Before And After ◽  
Red Grape

Abstract. The goals of this study were to determine and evaluate the bioaccessibility of total anthocyanin and procyanidin in apple (Amasya, Malus communis), red grape (Papazkarası, Vitis vinifera) and cinnamon (Cassia, Cinnamomum) using an in vitro static digestion system based on human gastrointestinal physiologically relevant conditions. Also, in vitro inhibitory effects of these foods on lipid (lipase) and carbohydrate digestive enzymes (α-amylase and α-glucosidase) were performed with before and after digested samples using acarbose and methylumbelliferyl oleate (4MUO) as the positive control. While the highest total anthocyanin content was found in red grape (164 ± 2.51 mg/100 g), the highest procyanidin content was found in cinnamon (6432 ± 177.31 mg/100 g) (p < 0.05). The anthocyanin bioaccessibilities were found as 10.2 ± 1%, 8.23 ± 0.64%, and 8.73 ± 0.70% in apple, red grape, and cinnamon, respectively. The procyanidin bioaccessibilities of apple, red grape, and cinnamon were found as 17.57 ± 0.71%, 14.08 ± 0.74% and 18.75 ± 1.49%, respectively. The analyzed apple, red grape and cinnamon showed the inhibitory activity against α-glucosidase (IC50 544 ± 21.94, 445 ± 15.67, 1592 ± 17.58 μg/mL, respectively), α-amylase (IC50 38.4 ± 7.26, 56.1 ± 3.60, 3.54 ± 0.86 μg/mL, respectively), and lipase (IC50 52.7 ± 2.05, 581 ± 54.14, 49.6 ± 2.72 μg/mL), respectively. According to our results apple, red grape and cinnamon have potential to inhibit of lipase, α-amylase and α-glucosidase digestive enzymes.

Total synthesis of melleumins A and B and their analogs: Determination of stereochemistry and Wnt signal inhibitory activity

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
M Ishibashi ◽  
S Hanazawa ◽  
Y Uchino ◽  
X Li ◽  
MA Arai
Keyword(s):  
Total Synthesis ◽  
Inhibitory Activity ◽  
Wnt Signal
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