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Structural and aggregation features of a human κ-Casein fragment with antitumor and cell-penetrating properties. / Chinak, Olga A.; Shernyukov, Andrey V.; Ovcherenko, Sergey S. et al.

In: Molecules, Vol. 24, No. 16, 2919, 12.08.2019.

Research output: Contribution to journalArticlepeer-review

Harvard

Chinak, OA, Shernyukov, AV, Ovcherenko, SS, Sviridov, EA, Golyshev, VM, Fomin, AS, Pyshnaya, IA, Kuligina, EV, Richter, VA & Bagryanskaya, EG 2019, 'Structural and aggregation features of a human κ-Casein fragment with antitumor and cell-penetrating properties', Molecules, vol. 24, no. 16, 2919. https://doi.org/10.3390/molecules24162919

APA

Chinak, O. A., Shernyukov, A. V., Ovcherenko, S. S., Sviridov, E. A., Golyshev, V. M., Fomin, A. S., Pyshnaya, I. A., Kuligina, E. V., Richter, V. A., & Bagryanskaya, E. G. (2019). Structural and aggregation features of a human κ-Casein fragment with antitumor and cell-penetrating properties. Molecules, 24(16), [2919]. https://doi.org/10.3390/molecules24162919

Vancouver

Chinak OA, Shernyukov AV, Ovcherenko SS, Sviridov EA, Golyshev VM, Fomin AS et al. Structural and aggregation features of a human κ-Casein fragment with antitumor and cell-penetrating properties. Molecules. 2019 Aug 12;24(16):2919. doi: 10.3390/molecules24162919

Author

Chinak, Olga A. ; Shernyukov, Andrey V. ; Ovcherenko, Sergey S. et al. / Structural and aggregation features of a human κ-Casein fragment with antitumor and cell-penetrating properties. In: Molecules. 2019 ; Vol. 24, No. 16.

BibTeX

@article{d7cd5b41bfac412a8df6aec3c0d53d2d,
title = "Structural and aggregation features of a human κ-Casein fragment with antitumor and cell-penetrating properties",
abstract = "Intrinsically disordered proteins play a central role in dynamic regulatory and assembly processes in the cell. Recently, a human κ-casein proteolytic fragment called lactaptin (8.6 kDa) was found to induce apoptosis of human breast adenocarcinoma MCF-7 and MDA-MB-231 cells with no cytotoxic activity toward normal cells. Earlier, we had designed some recombinant analogs of lactaptin and compared their biological activity. Among these analogs, RL2 has the highest antitumor activity, but the amino acid residues and secondary structures that are responsible for RL2's activity remain unclear. To elucidate the structure-activity relations of RL2, we studied the structural and aggregation features of this fairly large intrinsically disordered fragment of human milk κ-casein by a combination of physicochemical methods: NMR, paramagnetic relaxation enhancement (PRE), Electron Paramagnetic Resonance (EPR), circular dichroism, dynamic light scattering, atomic force microscopy, and a cytotoxic activity assay. It was found that in solution, RL2 exists as stand-alone monomeric particles and large aggregates. Whereas the disulfide-bonded homodimer turned out to be more prone to assembly into large aggregates, the monomer predominantly forms single particles. NMR relaxation analysis of spin-labeled RL2 showed that the RL2 N-terminal region, which is essential not only for multimerization of the peptide but also for its proapoptotic action on cancer cells, is more ordered than its C-terminal counterpart and contains a site with a propensity for ff-helical secondary structure.",
keywords = "Casein micelle, Dimerization, Disulfide bond, Intrinsically disordered protein, β-mercaptoethanol adduct, APOPTOSIS, intrinsically disordered protein, beta-mercaptoethanol adduct, dimerization, casein micelle, UNFOLDED PROTEINS, LACTAPTIN, PEPTIDE, NMR CHARACTERIZATION, disulfide bond, INTRINSICALLY DISORDERED PROTEINS, GROWTH, DYNAMICS",
author = "Chinak, {Olga A.} and Shernyukov, {Andrey V.} and Ovcherenko, {Sergey S.} and Sviridov, {Evgeniy A.} and Golyshev, {Victor M.} and Fomin, {Alexander S.} and Pyshnaya, {Inna A.} and Kuligina, {Elena V.} and Richter, {Vladimir A.} and Bagryanskaya, {Elena G.}",
year = "2019",
month = aug,
day = "12",
doi = "10.3390/molecules24162919",
language = "English",
volume = "24",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "16",

}

RIS

TY - JOUR

T1 - Structural and aggregation features of a human κ-Casein fragment with antitumor and cell-penetrating properties

AU - Chinak, Olga A.

AU - Shernyukov, Andrey V.

AU - Ovcherenko, Sergey S.

AU - Sviridov, Evgeniy A.

AU - Golyshev, Victor M.

AU - Fomin, Alexander S.

AU - Pyshnaya, Inna A.

AU - Kuligina, Elena V.

AU - Richter, Vladimir A.

AU - Bagryanskaya, Elena G.

PY - 2019/8/12

Y1 - 2019/8/12

N2 - Intrinsically disordered proteins play a central role in dynamic regulatory and assembly processes in the cell. Recently, a human κ-casein proteolytic fragment called lactaptin (8.6 kDa) was found to induce apoptosis of human breast adenocarcinoma MCF-7 and MDA-MB-231 cells with no cytotoxic activity toward normal cells. Earlier, we had designed some recombinant analogs of lactaptin and compared their biological activity. Among these analogs, RL2 has the highest antitumor activity, but the amino acid residues and secondary structures that are responsible for RL2's activity remain unclear. To elucidate the structure-activity relations of RL2, we studied the structural and aggregation features of this fairly large intrinsically disordered fragment of human milk κ-casein by a combination of physicochemical methods: NMR, paramagnetic relaxation enhancement (PRE), Electron Paramagnetic Resonance (EPR), circular dichroism, dynamic light scattering, atomic force microscopy, and a cytotoxic activity assay. It was found that in solution, RL2 exists as stand-alone monomeric particles and large aggregates. Whereas the disulfide-bonded homodimer turned out to be more prone to assembly into large aggregates, the monomer predominantly forms single particles. NMR relaxation analysis of spin-labeled RL2 showed that the RL2 N-terminal region, which is essential not only for multimerization of the peptide but also for its proapoptotic action on cancer cells, is more ordered than its C-terminal counterpart and contains a site with a propensity for ff-helical secondary structure.

AB - Intrinsically disordered proteins play a central role in dynamic regulatory and assembly processes in the cell. Recently, a human κ-casein proteolytic fragment called lactaptin (8.6 kDa) was found to induce apoptosis of human breast adenocarcinoma MCF-7 and MDA-MB-231 cells with no cytotoxic activity toward normal cells. Earlier, we had designed some recombinant analogs of lactaptin and compared their biological activity. Among these analogs, RL2 has the highest antitumor activity, but the amino acid residues and secondary structures that are responsible for RL2's activity remain unclear. To elucidate the structure-activity relations of RL2, we studied the structural and aggregation features of this fairly large intrinsically disordered fragment of human milk κ-casein by a combination of physicochemical methods: NMR, paramagnetic relaxation enhancement (PRE), Electron Paramagnetic Resonance (EPR), circular dichroism, dynamic light scattering, atomic force microscopy, and a cytotoxic activity assay. It was found that in solution, RL2 exists as stand-alone monomeric particles and large aggregates. Whereas the disulfide-bonded homodimer turned out to be more prone to assembly into large aggregates, the monomer predominantly forms single particles. NMR relaxation analysis of spin-labeled RL2 showed that the RL2 N-terminal region, which is essential not only for multimerization of the peptide but also for its proapoptotic action on cancer cells, is more ordered than its C-terminal counterpart and contains a site with a propensity for ff-helical secondary structure.

KW - Casein micelle

KW - Dimerization

KW - Disulfide bond

KW - Intrinsically disordered protein

KW - β-mercaptoethanol adduct

KW - APOPTOSIS

KW - intrinsically disordered protein

KW - beta-mercaptoethanol adduct

KW - dimerization

KW - casein micelle

KW - UNFOLDED PROTEINS

KW - LACTAPTIN

KW - PEPTIDE

KW - NMR CHARACTERIZATION

KW - disulfide bond

KW - INTRINSICALLY DISORDERED PROTEINS

KW - GROWTH

KW - DYNAMICS

UR - http://www.scopus.com/inward/record.url?scp=85070725238&partnerID=8YFLogxK

U2 - 10.3390/molecules24162919

DO - 10.3390/molecules24162919

M3 - Article

C2 - 31408975

AN - SCOPUS:85070725238

VL - 24

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 16

M1 - 2919

ER -

ID: 21238269