ABSTRACT
Molecular conformational engineering is to engineer flexible non-functional molecules into unique conformations to create novel functions just like natural proteins fold. Obviously, it is a grand challenge with tremendous opportunities. Based on the facts that natural proteins are only marginally stable with a net stabilizing energy roughly equivalent to the energy of two hydrogen bonds, and the energy barriers for the adatom diffusion of some metals are within a similar range, we propose that metal nanoparticles can serve as a general replacement of protein scaffolds to conformationally engineer protein fragments on the surface of nanoparticles. To prove this hypothesis, herein, we successfully restore the antigen-recognizing function of the flexible peptide fragment of a natural anti-lysozyme antibody on the surface of silver nanoparticles, creating a silver nanoparticle-base artificial antibody (Silverbody). A plausible mechanism is proposed, and some general principles for conformational engineering are summarized to guide future studies in this area.
ABSTRACT
OBJECTIVE: This study aimed to determine the therapeutic effectiveness of tuberculous aortic aneurysms (TBAAs) and the risk factors for mortality. METHODS: We reviewed all case reports of TBAAs treated with open surgery or endovascular aneurysm repair (EVAR) from online database in 1996-2021. Only thoracic and abdominal aortic aneurysms were included. RESULTS: Eighty cases of open surgery and 42 cases of EVAR were included. The 2-year mortality and perioperative mortality rates of open surgery were 11.3% and 10.0%, respectively. Emergent open surgery had a significantly higher mortality (25.0%) than non-emergent open surgery (6.7%). In the EVAR group, 2-year mortality, perioperative mortality, and TBAA-related mortality were 16.7%, 4.8%, and 10.0%, respectively. Patients with typical tuberculosis (TB) symptoms before EVAR had a significantly higher TBAA-related mortality (35.0%) than patients with no typical TB symptoms before EVAR (0%). In the open surgery group, the rate of TB recurrence (2.7% vs 2.4%) and aneurysm recurrence (8.1% vs 7.3%) were quite close between preoperative anti-TB-treated and postoperative anti-TB-treated cases. However, in the EVAR group, TB recurrence (8.7% vs 0%) and aneurysm recurrence (12.5% vs 6.25%) were more common in postoperative anti-TB-treated cases. CONCLUSION: Open surgery was accompanied by higher perioperative mortality, whereas EVAR was followed with higher TBAA-related mortality. Emergent surgical choices of open surgery may be associated with high perioperative mortality. Typical TB symptoms before EVAR are a significant risk factor for mortality after EVAR. Early anti-TB treatment should be administered if EVAR is the surgical option.
Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Tuberculosis , Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Endovascular Procedures/adverse effects , Humans , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Treatment Outcome , Tuberculosis/etiology , Tuberculosis/surgeryABSTRACT
Many efforts have been made to develop inhibitors of MDM2 as potential drugs for cancer therapy. In this work, we use our previous developed conformational engineering technique to stabilize the binding conformation of the p53 transcription activation domain (TAD) peptide on gold nanoparticles (AuNPs), and create an AuNP-based anti-MDM2 artificial antibody, denoted as anti-MDM2 Goldbody, that specifically binds MDM2. Though the free TAD peptide is unstructured, circular dichroism (CD) spectra confirm that its α-helical conformation in the original p53 protein is restored on the anti-MDM2 Goldbody, and surface plasmon resonance (SPR) experiments confirm that there is strong specific interaction between the anti-MDM2 Goldbody and MDM2, demonstrating the anti-MDM2 Goldbody as a potential inhibitor of MDM2. This work demonstrates that the conformational engineering technique is not limited to the antigen-antibody systems, but can also be applied more widely in other protein-protein interfaces to create increasingly more artificial proteins for various biomedical applications.
