Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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.
Язык оригинала | английский |
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Страницы (с-по) | 10900-10907 |
Число страниц | 8 |
Журнал | Journal of Medicinal Chemistry |
Том | 64 |
Номер выпуска | 15 |
Дата раннего онлайн-доступа | 16 июл 2021 |
DOI | |
Состояние | Опубликовано - 12 авг 2021 |
ID: 82306289