Study on the Materials Formed by Self‐Assembling Hydrophobic, Aromatic Peptides Dedicated to Be Used for Regenerative Medicine

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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.

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

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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

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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.

“…showed that the incorporation of one cysteine residue to the C‐terminal position in FF leads to nanospheres instead to typically observed fibers . In our previous study, we investigated the self‐assembling properties of several homomeric aromatic dipeptides (containing two identical residues) and of peptides with two identical aromatic residues and cysteine or methionine and we also found that incorporation of cysteine residue into peptide chain can change the morphology of aggregates.…”

Section: Introductionmentioning

confidence: 94%

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

Lipiński

Waśko

Walczak

et al. 2019

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The aim of the study was the assessment of the ability of short peptides to form aggregates under physiological conditions. The dipeptides studied were derived from different aromatic amino acids (heteroaromatic peptides). Tripeptides were obtained from two distinct aromatic amino acids and cysteine or methionine residue in the C‐terminal, N‐terminal, or central position. The ability of the peptides to form fibrous aggregates under physiological conditions was evaluated using three independent methods: the Congo Red assay, the Thioflavin T assay, and microscopic examinations using normal and polarized light. Materials potentially useful for regenerative medicine were selected based on their cytotoxicity to the endothelial cell line EA.hy 926 and physicochemical properties of films formed by peptides. The required parameters of biocompatibility were fulfilled by H−PheCysTrp−OH, H−PheCysTyr−OH, H−PheTyrMet−OH, and H−TrpTyr−OH.