24 research outputs found

    Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection

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    SummarySexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention

    The Use of Phage-Displayed Peptide Libraries to Develop Tumor-Targeting Drugs

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    Monoclonal antibodies have been successfully utilized as cancer-targeting therapeutics and diagnostics, but the efficacies of these treatments are limited in part by the size of the molecules and non-specific uptake by the reticuloendothelial system. Peptides are much smaller molecules that can specifically target cancer cells and as such may alleviate complications with antibody therapy. Although many endogenous and exogenous peptides have been developed into clinical therapeutics, only a subset of these consists of cancer-targeting peptides. Combinatorial biological libraries such as bacteriophage-displayed peptide libraries are a resource of potential ligands for various cancer-related molecular targets. Target-binding peptides can be affinity selected from complex mixtures of billions of displayed peptides on phage and further enriched through the biopanning process. Various cancer-specific ligands have been isolated by in vitro, in vivo, and ex vivo screening methods. As several peptides derived from phage-displayed peptide library screenings have been developed into therapeutics in current clinical trials, which validates peptide-targeting potential, the use of phage display to identify cancer-targeting therapeutics should be further exploited

    Impact of processing on the chemical and electronic properties of phenyl-C-61-butyric acid methyl ester

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    For the comparison of solution-processed to evaporated materials in organic optoelectronic devices, phenyl-C-61-butyric acid methyl ester (PCBM) has been claimed to be a suitable material. However, we ascertained differences between spin-coated and vacuum sublimed thin films. In this contribution, we thoroughly investigate the effects of thermal evaporation of PCBM in a strongly interdisciplinary approach, applying physical characterization techniques such as photoelectron (PES) and infrared (IR) spectroscopy in combination with further chemical analysis using thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC) and ultra-performance liquid chromatography-coupled mass spectrometry (UPLC-MS), as well as proton nuclear magnetic resonance spectroscopy (H-1-NMR). The methods were applied to thin films prepared by solution-based deposition techniques and by thermal evaporation. Additionally, comparison to an evaporated C-60 film and the crucible residues is carried out. Changes in the IR spectrum of the PCBM films already indicate a change in the molecular structure of PCBM. The UPLC chromatogram of the redissolved organic film proves the formation of several molecular species, including bare C-60. However, the effect of degradation on the electronic properties was found to be limited, as an almost unchanged ionization potential of 6.1 eV was determined with UPS for both the solution processed as well as the evaporated films. Also bulk-heterojunction (BHJ) solar cells fabricated using pure and thermally treated PCBM showed the same J-V characteristics under illumination
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