@article{heldt_gurgel_jaykus_carbonell_2012, title={Porcine parvovirus removal using trimer and biased hexamer peptides}, volume={7}, ISSN={1860-6768}, url={http://dx.doi.org/10.1002/biot.201000397}, DOI={10.1002/biot.201000397}, abstractNote={Assuring the microbiological safety of biological therapeutics remains an important concern. Our group has recently reported small trimeric peptides that have the ability to bind and remove a model nonenveloped virus, porcine parvovirus (PPV), from complex solutions containing human blood plasma. In an effort to improve the removal efficiency of these small peptides, we created a biased library of hexamer peptides that contains two previously reported trimeric peptides designated WRW and KYY. This library was screened and several hexamer peptides were discovered that also removed PPV from solution, but there was no marked improvement in removal efficiency when compared to the trimeric peptides. Based on simulated docking experiments, it appeared that hexamer peptide binding is dictated more by secondary structure, whereas the binding of trimeric peptides is dominated by charge and hydrophobicity. This study demonstrates that trimeric and hexameric peptides may have different, matrix-specific roles to play in virus removal applications. In general, the hexamer ligand may perform better for binding of specific viruses, whereas the trimer ligand may have more broadly reactive virus-binding properties.}, number={4}, journal={Biotechnology Journal}, publisher={Wiley}, author={Heldt, Caryn L. and Gurgel, Patrick V. and Jaykus, Lee-Ann and Carbonell, Ruben G.}, year={2012}, month={Apr}, pages={558–565} }
 @article{heldt_gurgel_jaykus_carbonell_2009, title={Influence of Peptide Ligand Surface Density and Ethylene Oxide Spacer Arm on the Capture of Porcine Parvovirus}, volume={25}, ISSN={["1520-6033"]}, DOI={10.1002/btpr.236}, abstractNote={In previous work, we identified two trimeric peptide ligands (designated WRW and KYY), which bound specifically to porcine parvovirus (PPV) and demonstrated their ability to capture and remove the virus from solutions containing 7.5% human blood plasma. This article examines the influences of peptide density and the presence of an ethylene oxide spacer arm on the efficiency of virus capture using these two ligands. The WRW peptide bound the most virus from plasma solutions at the lowest peptide density tested (0.008 mmol/g dry resin), and binding was enhanced by the presence of the spacer arm. On the other hand, the KYY peptide bound the most viruses at the same low peptide density, but it performed better in the absence of the spacer arm. Of the two, the binding efficiency of the WRW peptide was more sensitive to peptide density and spacer arm presence. These results indicate that low peptide densities enhance binding selectivity, facilitating specific peptide-virus binding even in the presence of plasma proteins which can theoretically bind nonspecifically.}, number={5}, journal={BIOTECHNOLOGY PROGRESS}, author={Heldt, Caryn L. and Gurgel, Patrick V. and Jaykus, Lee-Ann and Carbonell, Ruben G.}, year={2009}, pages={1411–1418} }
 @article{heldt_gurgel_jaykus_carbonell_2008, title={Identification of trimeric peptides that bind porcine parvovirus from mixtures containing human blood plasma}, volume={24}, ISSN={["1520-6033"]}, DOI={10.1021/bp070412c}, abstractNote={Virus contamination in human therapeutics is of growing concern as more therapeutic products from animal or human sources come into the market. All biopharmaceutical processes are required to have at least two distinct viral clearance steps to remove viruses. Most of these steps work well for enveloped viruses and large viruses, whether enveloped or not. That leaves a class of small non-enveloped viruses, like parvoviruses and hepatitis A, which are not easily removed by these typical steps. In this study, we report the identification of trimeric peptides that bind specifically to porcine parvovirus (PPV) and their potential use to remove this virus from process solutions. All of the trimeric peptides isolated completely removed all detectable PPV from buffer in the first nine column volumes, corresponding to a clearance of 4.5-5.5 log of infectious virus. When the virus was spiked into a more complex matrix consisting of 7.5% human blood plasma, one of the trimers, WRW, was able to remove all detectable PPV in the first three column volumes, after which human blood plasma began to interfere with the binding of the virus to the peptide resin. These trimer resins removed considerably more virus than weak ion exchange resins. The results of this work indicate that small peptide ligand resins have the potential to be used in virus removal processes where removal of contaminating virus is necessary to ensure product safety.}, number={3}, journal={BIOTECHNOLOGY PROGRESS}, author={Heldt, Caryn L. and Gurgel, Patrick V. and Jaykus, Lee-Ann and Carbonell, Ruben G.}, year={2008}, pages={554–560} }
 @article{heldt_hernandez_mudiganti_gurgel_brown_carbonell_2006, title={A  colorimetric assay for viral agents that produce cytopathic effects}, volume={135}, DOI={10.1016/j.j.viromet.2006.01.022}, number={1}, journal={Journal of Virological Methods}, author={Heldt, C. L. and Hernandez, R. and Mudiganti, U. and Gurgel, P. V. and Brown, D. T. and Carbonell, R. G.}, year={2006}, pages={56–65} }