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Sun J.,Jilin University | Yu J.-S.,Tsinghua University | Yu Z.,Tsinghua University | Zha X.,Sichuan Tumor Hospital and Institute | Wu Y.,Jilin University
Journal of Chemical Thermodynamics | Year: 2012

The high-risk types of human papillomaviruses (HPV) HPV-16 and -18 are the predominant types associated with cervical cancer. HPV-16 and -18 account for about 50% and 20%, respectively, of cervical cancers worldwide. While the reason and molecular mechanism of the distinct prevalence and distributions between them remain poorly understood, the binding affinity of cell surface receptor with capsid proteins, especially L1, may be involved. We examined heparin binding with two synthetic peptides corresponding to the 14 amino acid C-terminal peptides of HPV-16 and -18 L1 with the goal of comparing the equivalent residues in different HPV types. Using isothermal titration calorimetry (ITC) and static right-angle light scattering (SLS), we determined the binding constant K, reaction enthalpy ΔH, and other thermodynamic parameters in the interaction. Especially, we assessed the role of specific residues in binding with heparin by comparing the NMR spectra of free and heparin-bound peptides. © 2011 Elsevier Ltd. All rights reserved.

Zhang H.,Jilin University | Wang Y.,Jilin University | Liu C.,Jilin University | Zhang L.,Jilin University | And 9 more authors.
Cancer Immunology, Immunotherapy | Year: 2012

Survivin is overexpressed in major types of cancer and is considered an ideal "universal" tumorassociated antigen that can be targeted by immunotherapeutic vaccines. However, its anti-apoptosis function raises certain safety concerns. Here, a new truncated human survivin, devoid of the anti-apoptosis function, was generated as a candidate tumor vaccine. Interleukin 2 (IL-2) has been widely used as an adjuvant for vaccination against various diseases. Meanwhile, the DNA prime and recombinant adenovirus (rAd) boost heterologous immunization strategy has been proven to be highly effective in enhancing immune responses. Therefore, the efficacy of a new cancer vaccine based on a truncated form of survivin, combined with IL-2, DNA prime, and rAd boost, was tested. As prophylaxis, immunization with the DNA vaccine alone resulted in a weak immune response and modest anti-tumor effect, whereas the tumor inhibition ratio with the DNA vaccine administered with IL-2 increased to 89 % and was further increased to nearly 100 % by rAd boosting. Moreover, complete tumor rejection was observed in 5 of 15 mice. Efficacy of the vaccine administered therapeutically was enhanced by nearly 300 % when combined with carboplatin. These results indicated that vaccination with a truncated survivin vaccine using DNA prime-rAd boost combined with IL-2 adjuvant and carboplatin represents an attractive strategy to overcoming immune tolerance to tumors and has potential therapeutic benefits in melanoma cancer. © Springer-Verlag 2012.

Fu D.-Y.,Jilin University | Jin S.,Jilin University | Zheng D.-D.,Jilin University | Zha X.,Sichuan Tumor Hospital and Institute | Wu Y.,Jilin University
ACS Medicinal Chemistry Letters | Year: 2015

A new 14 peptide, originating essentially from the helix 5 of HPV 16L1, illustrates an IC50 of 19.38 nM for the inhibition of HPV 16 L1 pentamer formation, which is highly efficient for targeting a specific protein segment. In addition, mechanism studies reveal that the length, sequence, and the folding of the peptide are critical factors for its inhibition. Particularly, the peptide shows similar inhibition against the pentamer formation of HPV 58L1, although it is designed specially for HPV 16 L1. This study opens a way for the development of high-efficiency, broad-spectrum inhibitors as a new class of anti-HPV agents, which could be extended to the treatment of other virus types. © 2015 American Chemical Society.

Pan D.,Jilin University | Zha X.,Sichuan Tumor Hospital and Institute | Yu X.,Jilin University | Wu Y.,Jilin University
Protein Expression and Purification | Year: 2016

The major recombinant capsid protein L1 of human papillomavirus (HPV) is widely used to produce HPV prophylactic vaccines. However, the quality of soluble and active expression of L1 in Escherichia coli was below the required amount. Coexpression with the chaperonin GroEL/ES enhanced L1 expression. Overexpressing GroEL/ES increased the soluble expression level of glutathione S-transferase-fused L1 (GST-L1) by approximately ∼3 fold. The yield of HPV type 16 L1 pentamer (L1-p) was ∼2 fold higher than that in a single expression system after purification through size-exclusion chromatograph. The expression and purification conditions were then optimized. The yield of L1-p was enhanced by ∼5 fold, and those of HPV types 18 and 58 L1-p increased by ∼3 and ∼2 folds, respectively, compared with that in the single expression system. Coexpressing the mono-site mutant HPV16 L1 L469A with GroEL/ES increased L1-p yield by ∼7 fold compared with strains expressing the wild-type L1 gene. L1-p was then characterized using circular dichroism spectra, UV-vis cloud point, dynamic light scattering and transmission electron microscope analyses. Results indicated that the conformation and biological characteristics of L1-p were identical to that of native L1. Hence, overexpressing chaperonin in E. coli can increase the expression level of GST-L1 and L1-p production after purification. This finding may contribute to the development of a platform for prophylactic HPV vaccines. © 2015 Published by Elsevier Inc.

Zheng D.-D.,Jilin University | Pan D.,Jilin University | Zha X.,Jilin University | Zha X.,Sichuan Tumor Hospital and Institute | And 3 more authors.
Chemical Communications | Year: 2013

The recombinant GST fusion protein HPV 16 L1 from E. coli was proved to exist as a monomer rather than a pentamer, providing the possibility of real-time monitoring of the pentamer formation in vitro. Time-dependent kinetic studies of the process were performed for the first time by using static light scattering and western blot analysis, where the essential factors were revealed, offering a new biotechnical approach for virus control and/or the development of anti-viral agents. © The Royal Society of Chemistry 2013.

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