New peptide inhibitors modulate the self-assembly of islet amyloid polypeptide residues 11–20 in vitro

Mao, Yexuan; Yu, Lanlan; Yang, Ran; Ma, Chuanguo; Qu, Lingbo; Harrington, Peter de B.

doi:10.1016/j.ejphar.2017.03.015

Cited by 11 publications

(10 citation statements)

References 31 publications

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“…[31] The linear regression equation was established and listed in Table 2, and the types of binding events were determined by the principles of thermodynamics. [30] The results showed that the interaction between hIAPP [11][12][13][14][15][16][17][18][19][20] and these lipopeptide inhibitors is all spontaneous exothermic processes because of the negative change in Gibbs free energy and enthalpy changes. The values of ΔH and ΔS are negative, implying that these peptides bind to hIAPP [11][12][13][14][15][16][17][18][19][20] not only by means of van der Waals force but also by hydrogen bonding.…”

Section: Thermodynamic Parameters By Mstmentioning

confidence: 99%

“…On the basis of our previous study about different synthesized peptides modulating the self-assembly [30] of hIAPP [11][12][13][14][15][16][17][18][19][20] , most of the inhibitors that could effectively inhibit amyloid formation possess hydrophobic amino acids. Hence, in this study, several potential lipopeptide inhibitors containing hydrophobic alkyl chains and hydrophilic amino acids as head group have been engineered and synthesized, Cx-RRRR-NH 2 (x = 4, 6, 8, 10, 12, and 14; lipopeptides with x carbon atoms) and C14-Rn-NH 2 (n = 2, 3, 4, and 5; lipopeptides with n arginines) ( Figure 1).…”

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confidence: 99%

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Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Mao

et al. 2017

Journal of Peptide Science

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Type 2 diabetes mellitus, a kind of conformational disease, has become an epidemic disease, which seriously endangers the quality of life and health of human beings. The deposition of human islet amyloid polypeptide (hIAPP) has been considered as one of the major pathological features of type 2 diabetes mellitus. As lipopeptides have some hydrophobic groups, which are similar to the reported aggregation inhibitors, and some lipopeptides could prevent cells from depositing of amyloid fibrils, several potential lipopeptide inhibitors have been engineered and synthesized, which have been assessed for their inhibitory effect in preventing amyloid fibrils formation of hIAPP [11][12][13][14][15][16][17][18][19][20] by using the conventional thioflavin-T fluorescence assay and new technique microscale thermophoresis (MST). The final amyloid fibrils of hIAPP [11][12][13][14][15][16][17][18][19][20] were characterized by transmission electron microscopy. Results suggested that with the increasing length of alkyl chain, the antiaggregation efficiency of lipopeptide inhibitors towards hIAPP 11-20 increased gradually.Meanwhile, the amount of arginines, which represent the head groups of lipopeptides, may also have some influence. The binding events also showed that the inhibitory efficiency of these lipopeptide inhibitors was enhanced with the increase of affinities between lipopeptides and hIAPP [11][12][13][14][15][16][17][18][19][20] , which were obtained from MST. This study demonstrated the efficiency of lipopeptides in inhibiting the aggregation of hIAPP [11][12][13][14][15][16][17][18][19][20] and proved that MST could be regarded as an appropriate and rapid method to screen potential inhibitors of hIAPP [11][12][13][14][15][16][17][18][19][20] or other amyloid proteins. This study also broadens the types of inhibitors on inhibiting amyloid formation of hIAPP.

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Section: Thermodynamic Parameters By Mstmentioning

confidence: 99%

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confidence: 99%

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Mao

et al. 2017

Journal of Peptide Science

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“…Binding is detected by a quantification of the change in the normalised fluorescence. MST has been previously successfully used to detect binding of inhibitors to IAPP11-20 and other amyloids [55][56][57]. To monitor IAPP, we used bIAPP at a 1:9 ratio with IAPP (4 M IAPP overall), and avidin fluorescein.…”

Section: Pvp10-iapp Interaction Kd Determinationmentioning

confidence: 99%

“…IAPP11-20 or tau fibrils,) but also for non-amyloid systems (e.g. the Ser/Thr kinase p38 and its inhibitor BIRB-796, SNARE-liposome complexes, and the -lactamase TEM-1 with its inhibitor BLIP) [55,56,59,60]. In the case of TEM-1, it was suggested to be due to a conformational change of TEM-1 when bound by BLIP.…”

Section: Pvp10-iapp Interaction Kd Determinationmentioning

confidence: 99%

Multiphasic effect of vinyl pyrrolidone polymers on amyloidogenesis, from macromolecular crowding to inhibition

Berwick

Vaux

Jean

2018

Biochemical Journal

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Deposition of misfolded amyloid polypeptides, associated with cell death, is the hallmark of many degenerative diseases (e.g. type II diabetes mellitus and Alzheimer's disease). In vivo, cellular and extracellular spaces are occupied by a high volume fraction of macromolecules. The resulting macromolecular crowding energetically affects reactions. Amyloidogenesis can either be promoted by macromolecular crowding through the excluded volume effect or inhibited due to a viscosity increase reducing kinetics. Macromolecular crowding can be mimicked in vitro by the addition of non-specific polymers, e.g. Ficoll, dextran and polyvinyl pyrrolidone (PVP), the latter being rarely used to study amyloid systems. We investigated the effect of PVP on amyloidogenesis of full-length human islet amyloid polypeptide (involved in type II diabetes) using fibrillisation and surface activity assays, ELISA, immunoblot and microscale thermophoresis. We demonstrate that high molecular mass PVP360 promotes amyloidogenesis due to volume exclusion and increase in effective amyloidogenic monomer concentration, like other crowders, but without the confounding effects of viscosity and surface activity. Interestingly, we also show that low molecular mass PVP10 has unique inhibitory properties as inhibition of fibril elongation occurs mainly in the bulk solution and is due to PVP10 directly and strongly interacting with amyloid species rather than the increase in viscosity typically associated with macromolecular crowding. In vivo, amyloidogenesis might be affected by the properties and proximity of endogenous macromolecular crowders, which could contribute to changes in associated pathogenesis. More generally, the PVP10 molecular backbone could be used to design small compounds as potential inhibitors of toxic species formation.

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“…Hence, there is an urgent need for potent inhibitors of the process producing these pathogenic fibrils. In line with this, some inhibitors, including the peptides derived from the various secondary recognition elements along the amylin peptide chain [15][16][17] , engineered peptides [18][19][20] , constrained peptides [21][22][23][24][25][26][27] , small molecules 28,29 and natural products [30][31][32] , have been reported. Many of these inhibitors are specific in their activity; however, a good number of them have exhibited dual inhibitory activity such that they can inhibit amyloid aggregation of multiple classes of proteins non-specifically [32][33][34][35] .…”

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confidence: 93%

γ-AApeptides–based Small Molecule Ligands That Disaggregate Human Islet Amyloid Polypeptide

Bolarinwa

Khadka

et al. 2020

Sci Rep

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the abnormal folding and aggregation of functional proteins into amyloid is a typical feature of many age-related diseases, including type ii diabetes. Growing evidence has revealed that the prevention of aggregate formation in culprit proteins could retard the progression of amyloid diseases. Human Amylin, also known as human islet amyloid polypeptide (hiApp), is the major factor for categorizing Type II diabetes as an amyloid disease. Specifically, hIAPP has a great aggregation potential, which always results in a lethal situation for the pancreas. Many peptide inhibitors have been constructed from the various segments of the full-length hiApp peptide; however, only a few have their origin from the screening of combinatorial peptidomimetic library. In this study, based on HW-155, which was previously discovered from a one-bead-one compound (oBoc) library to inhibit Aβ 40 aggregation, we investigated eight (8) analogues and evaluated their amyloid-prevention capabilities for inhibiting fibrillization of hIAPP. Characterization studies revealed that all analogues of HW-155, as well as HW-155, were effective inhibitors of the fibril formation by hIAPP .

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New peptide inhibitors modulate the self-assembly of islet amyloid polypeptide residues 11–20 in vitro

Cited by 11 publications

References 31 publications

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Design and study of lipopeptide inhibitors on preventing aggregation of human islet amyloid polypeptide residues 11‐20

Multiphasic effect of vinyl pyrrolidone polymers on amyloidogenesis, from macromolecular crowding to inhibition

γ-AApeptides–based Small Molecule Ligands That Disaggregate Human Islet Amyloid Polypeptide

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