CHURA-CHAMBI, ROSA M.ARCURI, HELEN A.LINO, FELIPEVERSATI, NATANPALMA, MARIO S.FAVARO, DENIZE C.MORGANTI, LIGIA2017-01-182017-01-182017CHURA-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. <b>Biotechnology and Applied Biochemistry</b>, v. 64, n. 3, p. 356-363, 2017. DOI: <a href="https://dx.doi.org/10.1002/bab.1503">10.1002/bab.1503</a>. Disponível em: http://repositorio.ipen.br/handle/123456789/26990.0885-4513http://repositorio.ipen.br/handle/123456789/26990Endostatin (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.356-363closedAccessmolecular structureprotein structureangiogenesisapoptosisdichroismsimulationpurificationelectrophoresisfluorescence spectroscopyArtigo de periódico36410.1002/bab.1503https://orcid.org/0000-0002-7870-179319.35