作者: Cozine, Taryn ; Gollapudi, Deepika ; Lei, Q. Paula ; Schneck, Nicole A. ; Ivleva, Vera B. ; Ragheb, Daniel ; Patel, Aakash ; Gowetski, Daniel B. ; Barefoot, Nathan ; Cai, Cindy X.

For conjugated HIV-1 fusion peptide vaccine development, recombinant Tetanus toxoid heavy chain fragment C (rTTHC) was applied as a carrier protein to boost peptide immunogenicity. Understanding the characteristics of rTTHC is the first step prior to the peptide conjugation. A comprehensive mass spectrometry (MS) characterization was performed on E. coli expressed rTTHC during its purification process. Intact mass along with peptide mapping analysis discovered the existence of three cysteine modification forms: glutathionylation, trisulfide bond modification, and disulfide bond shuffling, in correlation to a three-peak profile during a hydrophobic interaction chromatography (HIC) purification step. Coexistence of these multiple oxidative forms indicated that the active thiols underwent redox reaction in the rTTHC material. Identity confirmation of the rTTHC carrier protein by MS analysis provided pivotal guidance to assess the purification step and helped ensure that vaccine development could proceed.

2019-12-09·Angewandte Chemie International Edition1区 · 化学

A DNA–Azobenzene Nanopump Fueled by Upconversion Luminescence for Controllable Intracellular Drug Release

1区 · 化学

Article

作者: He, Yuling ; Zhang, Xiaobo ; Zhang, Yue ; Song, Guobin ; Ju, Huangxian ; Liu, Ying

AbstractStimulus‐responsive drug release possesses considerable significance in cancer therapy. This work reports an upconversion‐luminescence‐fueled DNA–azobenzene nanopump for rapid and efficient drug release. The nanopump is constructed by assembling the azobenzene‐functionalized DNA strands on upconversion nanoparticles (UCNPs). Doxorubicin (DOX) is loaded in the nanopump by intercalation in the DNA helix. Under NIR light, the UCNPs emit both UV and visible photons to fuel the continuous photoisomerization of azo, which acts as an impeller pump to trigger cyclic DNA hybridization and dehybridization for controllable DOX release. In a relatively short period, this system demonstrates 86.7 % DOX release. By assembling HIV‐1 TAT peptide and hyaluronic acid on the system, targeting of the cancer‐cell nucleus is achieved for perinuclear aggregation of DOX and enhanced anticancer therapy. This highly effective drug delivery nanopump could contribute to chemotherapy development.

2018-12-01·Proteins: Structure, Function, and Bioinformatics3区 · 生物学

Prediction of cross‐clade HIV‐1 T‐cell epitopes using immunoinformatics analysis

3区 · 生物学

Article

作者: Bolhassani, Azam ; Kardani, Kimia ; Namvar, Ali ; Khairkhah, Niloofar

AbstractEpitope mapping has emerged as a powerful tool to develop peptide vaccines against hypervariable viruses such as HIV. This method has led to stimulate a specific immune response and achieve advanced vaccine formulations. In this study, we identified peptides that were potentially immunostimulatory and highly conserved in HIV‐1 main group. The analyses included were CTL assay, Tap transport, and the potential allergenicity. The highest population coverage rate was also found for all potential T‐cell epitopes in 16 specified geographic regions of the world. The current study is the first attempt to explore peptide‐protein flexible docking across all the major epitopes of HIV‐1. Our data indicated that REV54‐63and VPU58‐66 with the highest epitope identification scores, GP16037‐46 and VPR38‐47 with the highest conservation (98.89%), and NEF134‐144 and GP16037‐46 epitopes with a higher quality of peptide‐protein interaction models in docking procedure were chosen as putative epitopes among all HLA class I epitopes. TAT40‐67, VPR65‐82, and VPU30‐44 with the highest score of binding affinity, VPR65‐82 with the highest conservation (97.55%), and GP160481‐498 epitope with a higher quality of peptide‐protein interaction models in docking procedure were determined as putative epitopes among all HLA‐DR epitopes. Furthermore, two epitopes of GP160481‐498 and VIF144‐159 were predicted to bind 22 and 21 HLA‐II alleles, respectively. Accumulative population coverage of potential helper T‐cell epitopes and CTL epitopes varied between 90.82% and 100%. Generally, these predicted highly immunogenic T‐cell epitopes can contribute to design HIV‐1 peptide vaccine candidates. Combination of bioinformatics tools with in vivo methods will be necessary for HIV‐1 vaccine development.

100 项与单价微粒多肽疫苗(United Biomedical, Inc.) 相关的药物交易

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