Publications on the discovery of theta defensins and the development of Orynotides

The biological properties of theta defensins including the peptides’ antimicrobial activities and immune modulatory functions have been reported. Recent studies have demonstrated that theta defensins and Orynotides modulate pro-inflammatory responses including those associated with chronic inflammation and they block cellular invasion and proliferation in certain autoimmune disseases. Ongoing studies on the immunomodulatory properties of our macrocyclic peptides are aimed toward the development of novel treatments for autoimmune and inflammatory diseases. Selected publications are as follows:

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  1. Selsted, M. E., and Ouellette, A. J. (2005) Mammalian defensins in the antimicrobial immune response. Nature immunology 6, 551-557
  2. Selsted, M. E. (2004) Theta-defensins: cyclic antimicrobial peptides produced by binary ligation of truncated alpha-defensins. Current protein & peptide science 5, 365-371
  3. Tang, Y. Q., Yuan, J., Osapay, G., Osapay, K., Tran, D., Miller, C. J., Ouellette, A. J., and Selsted, M. E. (1999) A cyclic antimicrobial peptide produced in primate leukocytes by the ligation of two truncated alpha-defensins. Science 286, 498-502
  4. Tran, D., Tran, P. A., Tang, Y. Q., Yuan, J., Cole, T., and Selsted, M. E. (2002) Homodimeric theta-defensins from rhesus macaque leukocytes: isolation, synthesis, antimicrobial activities, and bacterial binding properties of the cyclic peptides. J Biol Chem 277, 3079-3084
  5. Selsted, M. E. (2007) A pocket guide to explorations of the defensin field. Current pharmaceutical design 13, 3061-3064
  6. Wohlford-Lenane, C. L., Meyerholz, D. K., Perlman, S., Zhou, H., Tran, D., Selsted, M. E., and McCray, P. B., Jr. (2009) Rhesus theta-defensin prevents death in a mouse model of severe acute respiratory syndrome coronavirus pulmonary disease. J Virol 83, 11385-11390
  7. Tongaonkar, P., Tran, P., Roberts, K., Schaal, J., Osapay, G., Tran, D., Ouellette, A. J., and Selsted, M. E. (2011) Rhesus macaque {theta}-defensin isoforms: expression, antimicrobial activities, and demonstration of a prominent role in neutrophil granule microbicidal activities. J Leukoc Biol 89, 283-290
  8. Lehrer, R. I., Cole, A. M., and Selsted, M. E. (2012) Theta-Defensins: cyclic peptides with endless potential. J Biol Chem 287, 27014-27019
  9. Schaal, J. B., Tran, D., Tran, P., Osapay, G., Trinh, K., Roberts, K. D., Brasky, K. M., Tongaonkar, P., Ouellette, A. J., and Selsted, M. E. (2012) Rhesus macaque theta defensins suppress inflammatory cytokines and enhance survival in mouse models of bacteremic sepsis. PLoS One 7, e51337
  10. Beringer, P. M., Bensman, T. J., Ho, H., Agnello, M., Denovel, N., Nguyen, A., Wong-Beringer, A., She, R., Tran, D. Q., Moskowitz, S. M., and Selsted, M. E. (2016) Rhesus theta-defensin-1 (RTD-1) exhibits in vitro and in vivo activity against cystic fibrosis strains of Pseudomonas aeruginosa. The Journal of antimicrobial chemotherapy 71, 181-188
  11. Tongaonkar, P., Trinh, K. K., Schaal, J. B., Tran, D., Gulko, P. S., Ouellette, A. J., and Selsted, M. E. (2015) Rhesus macaque theta-defensin RTD-1 inhibits proinflammatory cytokine secretion and gene expression by inhibiting the activation of NF-kappaB and MAPK pathways. J Leukoc Biol