Noncovalent inhibitors of human 20S and 26S proteasome based on trypsin inhibitor SFTI‐1

Dębowski, Dawid; Cichorek, M; Lubos, Marta; Wójcik, Sławomir; Łęgowska, Anna; Rolka, Krzysztof

doi:10.1002/bip.22886

Cited by 8 publications

(6 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These properties highlight the significant potential of SFTI‐1 variants as drug leads, and also as tools for chemical biology studies, where they can be used to explore the physiological roles of individual proteases [45, 47] . Furthermore, it is becoming increasingly clear that non‐proteinogenic amino acids can be introduced at several positions in the SFTI‐1 scaffold (Figure 5), which opens up new opportunities for fine‐tuning inhibitor activity and selectivity, [23, 27b, 33a, 36b, 40, 48] as well as the production of modified variants for mode of action studies.…”

Section: Sfti‐1 As a Template For Protease Inhibitor Engineeringmentioning

confidence: 99%

Sunflower Trypsin Inhibitor‐1 (SFTI‐1): Sowing Seeds in the Fields of Chemistry and Biology

2020

View full text Add to dashboard Cite

(Australia) with Prof. Robert Brownlee, and undertook postdoctoral studies with Prof. George Levy at Florida State and Syracuse Universities (USA). He moved to UQ in 1995 to set up abiomolecular NMR laboratory and is currently an Australian Research Council (ARC) Laureate Fellow,Director of the ARC Centre of Excellence for Innovations in Peptide and Protein Science, and aF ellow of the Australian Academyo fScience. His research focuses on applications of cyclic peptides, toxins, and NMR spectroscopy in drug design.

show abstract

Section: Sfti‐1 As a Template For Protease Inhibitor Engineeringmentioning

confidence: 99%

Sunflower Trypsin Inhibitor‐1 (SFTI‐1): Sowing Seeds in the Fields of Chemistry and Biology

2020

View full text Add to dashboard Cite

show abstract

“…2018 10.5603/FHC.a2018.0021 www.fhc.viamedica.pl the Bomirski hamster melanoma model to compare the biology of melanotic and amelanotic melanomas; this consists of two basic lines, melanotic Ma and amelanotic Ab, which arose as a consequence of spontaneous alteration from the Ma form. The change of a melanotic into an amelanotic melanoma results in growth rate acceleration, a lack of melanosomes, ultrastructural changes in cells [14], and a low rate of spontaneous apoptosis, as well as high susceptibility to induced apoptosis [15][16][17][18]. The amelanization of melanoma cells is not well understood.…”

Section: Introductionmentioning

confidence: 99%

Melanization of Bomirski hamster amelanotic melanoma cells (Ab line) depends on the type of culture medium

Skoniecka

Zauszkiewicz-Pawlak

Tymińska

et al. 2019

Folia Histochem Cytobiol.

View full text Add to dashboard Cite

Introduction. The effect of melanogenesis intensity on melanoma biology remains an open question, and the biological differences between melanotic and amelanotic melanoma cells have not yet been satisfactorily documented. As a result, the melanization of melanoma cells in in vitro cultures is not considered among experimental procedures. The aim of this study was to investigate the effect of the medium used to culture Bomirski amelanotic Ab melanoma cells on the melanogenesis process. Material and methods. Amelanotic melanoma cells (Ab) were cultured in two media recommended for in vitro melanoma cell cultures, RPMI and DMEM. The melanization was evaluated by determining the melanin and tyrosinase presence in the cells using spectrophotometrical and western blot methods, respectively. Changes in Ab melanoma cells' ultrastructure were determined using electron microscopy (EM). Results. The medium with higher level of tyrosine (DMEM) induced significant melanization of amelanotic melanoma cells (Ab) after only 24 h, while the RPMI medium, with a lower level of tyrosine, weakly affected melanin production. Melanization of Ab cells was paralleled by an increase in the amount of tyrosinase protein. Induced melanization was easily observed on EM-micrographs in the form of newly formed melanosomes containing melanin pigment. Melanosomes at stages from one (I) to four (IV) were observed. Conclusions. Culture medium has an important effect on the in vitro biology of amelanotic melanoma cells, since it can affect the rate of cellular melanization. The appropriate medium should be carefully selected, taking into account the known biology of the melanoma cells being used.

show abstract

“…All of them have a hydrophilic polyethylene glycol derivative, 8‐amino‐3,6‐dioxaoctanoyl group (O2Octa) attached to their N ‐terminal amino groups. This derivative was used in our previous research on noncovalent proteasome inhibitors, which were designed based on the primary structure of peptidic sunflower trypsin inhibitor SFTI‐1 …”

Section: Resultsmentioning

confidence: 99%

“…This derivative was used in our previous research on noncovalent proteasome inhibitors, which were designed based on the primary structure of peptidic sunflower trypsin inhibitor SFTI-1. [17,18] Second, the selected inhibitors were modified with different Nterminal acyl group having various length and chemical character ( Figure 2). Such a modification strategy was primarily inspired by the story about Fellutamide B.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of human constitutive 20S proteasome and 20S immunoproteasome with novel N‐terminally modified peptide aldehydes and their antitumor activity

et al. 2018

Self Cite

View full text Add to dashboard Cite

The conversion of primary structures of novel, highly selective and sensitive, internally quenched peptide substrates of the human 20S proteasome into peptide aldehydes is presented. Such covalent and reversible inhibitors differ in their primary structures and chemical moieties attached to their N‐terminal amino group. Inhibitory potency is primarily tested against proteolytic subunits of human constitutive 20S proteasome (β1c, β2c, and β5c subunits), but in some cases, also against 20S immunoproteasome β5i. Most of the peptide aldehydes act nonspecifically and bind equipotently to the corresponding proteolytic subunits of both forms of proteasome (β5c and β5i). Two inhibitors are 2.7‐times more specific for immunoproteasome over its constitutive counterpart. The antitumor activity of the selected inhibitors and MG132 (used here as the reference) is analyzed using MTT assay against nonmalignant human fetal osteoblastic hFOB 1.19, malignant human osteosarcoma MG‐63, human pancreatic cancer MiaPaCa‐2, and human acute leukemia Jurkat T cell lines. All inhibitors tested are able to decrease cell viability in a concentration‐dependent manner. One of the peptide aldehydes exerted stronger, as compared to the MG132, activity against human glioblastoma cell line U87‐MG. Moreover, its combination with dinaciclib, which is a novel, potent inhibitor of cyclin‐dependent kinases, reduces cellular metabolic activity more potently as compared to either proteasome inhibitor or dinaciclib alone.

show abstract

Noncovalent inhibitors of human 20S and 26S proteasome based on trypsin inhibitor SFTI‐1

Cited by 8 publications

References 43 publications

Sunflower Trypsin Inhibitor‐1 (SFTI‐1): Sowing Seeds in the Fields of Chemistry and Biology

Sunflower Trypsin Inhibitor‐1 (SFTI‐1): Sowing Seeds in the Fields of Chemistry and Biology

Melanization of Bomirski hamster amelanotic melanoma cells (Ab line) depends on the type of culture medium

Inhibition of human constitutive 20S proteasome and 20S immunoproteasome with novel N‐terminally modified peptide aldehydes and their antitumor activity

Contact Info

Product

Resources

About