Fibrous Aggregates of Short Peptides Containing Two Distinct Aromatic Amino Acid Residues

Lipiński, Wojciech P.; Waśko, Joanna; Walczak, Małgorzata; Frączyk, Justyna; Kamiński, Zbigniew J.; Gałęcki, Krystian; Draczyński, Zbigniew; Krucińska, Izabella; Kamińska, M.; Kolesińska, Beata

doi:10.1002/cbdv.201900339

Cited by 5 publications

(6 citation statements)

References 55 publications

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“…On the other hand, it was expected that it would be possible to test the influence of aromatic amino acids on the inhibition of β-secretase (BACE1) activity, which is known to hydrolyze beta-site amyloid precursor proteins, and the formation of β-amyloid structures results in the formation of insoluble amyloid deposits. It is known that both β-amyloid and other aggregates of their hot-spots contain aromatic amino acids [ 34 , 35 , 36 ].…”

Section: Resultsmentioning

confidence: 99%

1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

et al. 2021

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A series of new analogs of nitrogen mustards (4a–4h) containing the 1,3,5-triazine ring substituted with dipeptide residue were synthesized and evaluated for the inhibition of both acetylcholinesterase (AChE) and β-secretase (BACE1) enzymes. The AChE inhibitory activity studies were carried out using Ellman’s colorimetric method, and the BACE1 inhibitory activity studies were carried out using fluorescence resonance energy transfer (FRET). All compounds displayed considerable AChE and BACE1 inhibition. The most active against both AChE and BACE1 enzymes were compounds A and 4a, with an inhibitory concentration of AChE IC50 = 0.051 µM; 0.055 µM and BACE1 IC50 = 9.00 µM; 11.09 µM, respectively.

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Section: Resultsmentioning

confidence: 99%

1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

et al. 2021

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“…The use of three independent methods has avoided the problem that the fact that methods of studying weak interaction, including self‐organization processes, are associated with a high risk of false results. This approach turned out to be useful in our search for fragments responsible for insulin aggregation as well as in research on the influence of aromatic amino acids on the ability to aggregate short peptides [45–49] . Results of microscopic examination of complexes formed by fragments of amylin (18–22) H‐HSSNN‐OH; (23–27) H‐FGAIL‐OH, (33–37) H‐GSNTY‐NH 2 prone to aggregation with fragments: cyclic (1–7) H‐KCNTATC‐OH, (8–12) H‐ATQRL‐OH, (13–17) H‐ANFLV‐OH, (28–32) H‐SSTNV‐OH devoid of aggregation properties are shown in Figures 3–5.…”

Section: Resultsmentioning

confidence: 99%

Non‐Aggregating Amylin Fragments as an Inhibitors of the Aggregation Process of Susceptible to Aggregation Fragments 18–22, 23–27, and 33–37 of Hormone

Frączyk

Janczewski

Waśko

et al. 2021

Chemistry & Biodiversity

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Amylin aggregation is one of the factors in the development of diabetes mellitus, which is classified as a civilization disease. The aim of this research was to find whether non‐aggregating fragments 1–7, 8–12, 13–17 and 28–32 of amylin would inhibit the aggregation of the amyloidogenic cores 18–22, 23–27, 33–37 of hormone. In the study of the inhibitory potential of non‐aggregating amylin fragments, a set of independent methods were used to study aggregation properties (spectroscopic and fluorescence studies with the use of indicators, microscopic studies, circular dichroism studies) and the method of prediction of aggregation properties. The performed research allowed to select the cyclic fragment (1–7) H‐KCNTATC‐OH with disulfide bond as an inhibitor capable of inhibiting the aggregation of all amyloidogenic cores 18–22, 23–27, 33–37 of the hormone. Additionally, it was found that this peptide inhibits insulin hot spot aggregation, which may indicate its universal utility in inhibiting the process of aggregation of hormones regulating carbohydrate metabolism directly related to the development of diabetes. Research on the possibility of the extensive use of the cyclic fragment (1–7) of H‐KCNTATC‐OH as a peptide inhibitor of the polypeptide/protein aggregation process is ongoing.

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“…After 7 days of incubation, a solution of CR in phosphate buffer and/or Thioflavin T was added to the samples. Standard procedures were followed [38–40] …”

Section: Resultsmentioning

confidence: 99%

“…Standard procedures were followed. [38][39][40] Five of the tested peptides were found to have an inhibitory effect on the aggregating (18)(19)(20)(21)(22) HÀ HSSNNÀ OH fragment ( Figure 5). No inhibitory effect was noted for HÀ F(NÀ Me)GA(NÀ Me)ILÀ OH (6) in a complex with (18-22) HÀ HSSNNÀ OH.…”

Section: Resultsmentioning

confidence: 99%

N‐Methylated Analogs of hIAPP Fragments 18–22, 23–27, 33–37 Inhibit Aggregation of the Amyloidogenic Core of the Hormone

Rożniakowski

Gałęcki

Wietrzyk

et al. 2020

Chemistry & Biodiversity

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Amylin (hIAPP) aggregation leads to the formation of insoluble deposits and is one of the factors in the development of type II diabetes. The aim of this research was to find N-methylated analogs of the aggregating amylin fragments 18-22, 23-27, and 33-37, which would not themselves be susceptible to aggregation and would inhibit the aggregation of the amyloidogenic cores of the hormone. None of the analogs of fragment 18-22 containing one or two N-methylated amino acid residues showed any tendency to aggregate. Only the peptide HÀ F(NÀ Me)GA(NÀ Me) ILÀ OH (6) derived from the 23-27 hIAPP hot spot did not form fibrous structures. All analogs of the 33-37 amylin fragment were characterized by the ability to form aggregates, despite the presence of N-methylated amino acids in their structures. N-Methylated peptides 1-5 demonstrated inhibitory properties against the aggregation of fragment 18-22. Aggregation of the amyloidogenic core of 23-27 was significantly inhibited by N-methylated peptides 1-3 derived from the (18-22) HÀ HSSNNÀ OH fragment and by the HÀ F(N-Me)GA(NÀ Me)ILÀ OH (6) fragment derived from the 23-27 amylin hot spot. Fragment (33-37) HÀ GSNTYÀ NH 2 was found to be inhibited in the presence of N-methylated peptides 1-3 derived from the 18-22 fragment and by the double methylated peptide HÀ F(NÀ Me)GA(NÀ Me)ILÀ OH (6). Research on the possibility of using N-methylated analogs of amyloidogenic amylin cores as inhibitors of hormone aggregation is ongoing, with a focus on finding the minimum concentration of N-methylated peptides capable of inhibiting the aggregation of hIAPP hot spots.

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Fibrous Aggregates of Short Peptides Containing Two Distinct Aromatic Amino Acid Residues

Cited by 5 publications

References 55 publications

1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

1,3,5-Triazine Nitrogen Mustards with Different Peptide Group as Innovative Candidates for AChE and BACE1 Inhibitors

Non‐Aggregating Amylin Fragments as an Inhibitors of the Aggregation Process of Susceptible to Aggregation Fragments 18–22, 23–27, and 33–37 of Hormone

N‐Methylated Analogs of hIAPP Fragments 18–22, 23–27, 33–37 Inhibit Aggregation of the Amyloidogenic Core of the Hormone

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