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.
In: Journal of Medicinal Chemistry, Vol. 64, No. 15, 12.08.2021, p. 10900-10907.Research output: Contribution to journal › Article › peer-review
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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
N1 - Publisher Copyright: © 2021 American Chemical Society.
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