Structural studies of the protein endostatin in fusion with BAX BH3 death domain, a hybrid that presents enhanced antitumoral activity
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Biotechnology and Applied Biochemistry
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Endostatin (ES) is an antiangiogenic protein that exhibits
antitumor activity in animal models. However, the activity
observed in animals was not observed in human clinical trials.
ES-BAX is a fusion protein composed of two functional
domains: ES, which presents specificity and is internalized by
activated endothelial cells and the proapoptotic BH3 domain
of the protein BAX, a peptide inductor of cellular death when
internalized. We have previously shown (Chura-Chambi et al.,
Cell Death Dis, 5, e1371, 2014) that ES-BAX presents improved
antitumor activity in relation to wild-type ES. Secondary and
tertiary structures of ES-BAX are similar to ES, as indicated by
homology-modeling studies and molecular dynamics
simulations. Tryptophan intrinsic fluorescence and circular
dichroism spectroscopy corroborate these data. 15N HSQC
NMR indicates that ES-BAX is structured, but some ES
residues have suffered chemical shift perturbations,
suggesting that the BH3 peptide interacts with some parts of
the ES protein. ES and ES-BAX present similar stability to
thermal denaturation. The production of stable hybrid proteins
can be a new approach to the development of therapeutic
agents presenting specificity for tumoral endothelium and
improved antitumor effect.
Como referenciar
CHURA-CHAMBI, ROSA M.; ARCURI, HELEN A.; LINO, FELIPE; VERSATI, NATAN; PALMA, MARIO S.; FAVARO, DENIZE C.; MORGANTI, LIGIA. Structural studies of the protein endostatin in fusion with BAX BH3 death domain, a hybrid that presents enhanced antitumoral activity. Biotechnology and Applied Biochemistry, v. 64, n. 3, p. 356-363, 2017. DOI: 10.1002/bab.1503. Disponível em: http://repositorio.ipen.br/handle/123456789/26990. Acesso em: 30 Dec 2025.
Esta referência é gerada automaticamente de acordo com as normas do estilo IPEN/SP (ABNT NBR 6023) e recomenda-se uma verificação final e ajustes caso necessário.