Conformationally Constrained Peptides with High Affinity to the Vascular Endothelial Growth Factor

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Conformationally Constrained Peptides with High Affinity to the Vascular Endothelial Growth Factor. / Гурьянов, Иван Алексеевич ; Коржиков-Влах, Виктор Александрович; Bhattacharya, Madhushree; Biondi, Barbara; Masiero, Giulia; Formaggio, Fernando; Тенникова, Татьяна Борисовна ; Уртти, Арто Олави.

в: Journal of Medicinal Chemistry, Том 64, № 15, 12.08.2021, стр. 10900-10907.

Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование

BibTeX

@article{732eb4ce58b847e7a4f65906061c7d23,

title = "Conformationally Constrained Peptides with High Affinity to the Vascular Endothelial Growth Factor",

abstract = "The design of efficient vascular endothelial growth factor (VEGF) inhibitors is a high-priority research area aimed at the treatment of pathological angiogenesis. Among other compounds, v114∗ has been identified as a potent VEGF-binding peptide. In order to improve the affinity to VEGF, we built a conformational constrain in its structure. To this aim, Cα-tetrasubstituted amino acid Aib was introduced into the N-terminal tail, peptide loop, or C-terminal helix. NMR studies confirmed the stabilization of the helical conformation in proximity to the Aib residue. We found that the induction of the N-terminal helical structure or stabilization of the C-terminal helix can noticeably increase the peptide affinity to the VEGF. These peptides efficiently inhibited VEGF-stimulated cell proliferation as well. The insertion of the non-proteinogenic Aib residue significantly enhanced the stability of the peptides in the vitreous environment. Thus, these Aib-containing peptides are promising candidates for the design of VEGF inhibitors with improved properties.",

keywords = "пептиды, анти-VEGF, микромасштабный термофорез, терпия глазных болезней, ANGIOGENESIS, ASSAY, CIRCULAR-DICHROISM, COMPLEX, DESIGN, FIELD, MACULAR DEGENERATION, RECEPTOR, SPECTRA, SYSTEM",

author = "Гурьянов, {Иван Алексеевич} and Коржиков-Влах, {Виктор Александрович} and Madhushree Bhattacharya and Barbara Biondi and Giulia Masiero and Fernando Formaggio and Тенникова, {Татьяна Борисовна} and Уртти, {Арто Олави}",

note = "Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

month = aug,

day = "12",

doi = "10.1021/acs.jmedchem.1c00219",

language = "English",

volume = "64",

pages = "10900--10907",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "15",

}

RIS

TY - JOUR

T1 - Conformationally Constrained Peptides with High Affinity to the Vascular Endothelial Growth Factor

AU - Гурьянов, Иван Алексеевич

AU - Коржиков-Влах, Виктор Александрович

AU - Bhattacharya, Madhushree

AU - Biondi, Barbara

AU - Masiero, Giulia

AU - Formaggio, Fernando

AU - Тенникова, Татьяна Борисовна

AU - Уртти, Арто Олави

PY - 2021/8/12

Y1 - 2021/8/12

N2 - The design of efficient vascular endothelial growth factor (VEGF) inhibitors is a high-priority research area aimed at the treatment of pathological angiogenesis. Among other compounds, v114∗ has been identified as a potent VEGF-binding peptide. In order to improve the affinity to VEGF, we built a conformational constrain in its structure. To this aim, Cα-tetrasubstituted amino acid Aib was introduced into the N-terminal tail, peptide loop, or C-terminal helix. NMR studies confirmed the stabilization of the helical conformation in proximity to the Aib residue. We found that the induction of the N-terminal helical structure or stabilization of the C-terminal helix can noticeably increase the peptide affinity to the VEGF. These peptides efficiently inhibited VEGF-stimulated cell proliferation as well. The insertion of the non-proteinogenic Aib residue significantly enhanced the stability of the peptides in the vitreous environment. Thus, these Aib-containing peptides are promising candidates for the design of VEGF inhibitors with improved properties.

AB - The design of efficient vascular endothelial growth factor (VEGF) inhibitors is a high-priority research area aimed at the treatment of pathological angiogenesis. Among other compounds, v114∗ has been identified as a potent VEGF-binding peptide. In order to improve the affinity to VEGF, we built a conformational constrain in its structure. To this aim, Cα-tetrasubstituted amino acid Aib was introduced into the N-terminal tail, peptide loop, or C-terminal helix. NMR studies confirmed the stabilization of the helical conformation in proximity to the Aib residue. We found that the induction of the N-terminal helical structure or stabilization of the C-terminal helix can noticeably increase the peptide affinity to the VEGF. These peptides efficiently inhibited VEGF-stimulated cell proliferation as well. The insertion of the non-proteinogenic Aib residue significantly enhanced the stability of the peptides in the vitreous environment. Thus, these Aib-containing peptides are promising candidates for the design of VEGF inhibitors with improved properties.

KW - пептиды

KW - анти-VEGF

KW - микромасштабный термофорез

KW - терпия глазных болезней

KW - ANGIOGENESIS

KW - ASSAY

KW - CIRCULAR-DICHROISM

KW - COMPLEX

KW - DESIGN

KW - FIELD

KW - MACULAR DEGENERATION

KW - RECEPTOR

KW - SPECTRA

KW - SYSTEM

UR - https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.1c00219

UR - http://www.scopus.com/inward/record.url?scp=85111543342&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/cf06f6fc-c429-3712-9ac6-d2acee1da455/

U2 - 10.1021/acs.jmedchem.1c00219

DO - 10.1021/acs.jmedchem.1c00219

M3 - Article

VL - 64

SP - 10900

EP - 10907

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 15

ER -

ID: 82306289