Bioactive Peptides

Antimicrobial peptides, AMPs, have long been known to play roles in innate defense and have broad capability for antimicrobial, antiviral and anticancer activities. Peptides offer several advantages over other small molecule and large molecule biologics – including greater efficacy, selectivity and specificity relative to small organic molecules, better tissue penetration, and reduced immunogenicity and manufacturing costs relative to proteins/antibodies.

Plant-derived natural products have served as sources for new leads and inspiration for novel chemistries at the forefront of drug discovery. Plants have been relied upon for centuries for primary health care in developing nations, with 20 to 80% of the population of developing countries still relying on botanical products almost exclusively for primary health care, and have also contributed substantially to Western medicine. While tens of thousands of plant species are estimated to be used traditionally, only a small percentage has been screened for biological activity.

As antimicrobial peptides are ubiquitously expressed in plants for both signaling and defense, we posit the plant kingdom remains an untapped resource for the identification of new antimicrobial peptidyl species. Using the peptidomics platform developed in our laboratory, we aim to discover and characterize new botanical antimicrobial peptides through a rationalized hybrid bioassay-guided/top-down mass spectrometry-based platform. Harnessing the power of mass spectrometry-based peptidomics will open up the door for investigating purpose-guided plant extracts with a new lens, and has the potential to lead to the discovery of novel chemistries at the forefront of modern drug discovery.

There is a strong need for such novel compounds due to significant increases in resistance in different microbial strains and cells against available therapeutic compounds. This exploration of natural resources will be a source of bioactive compounds that may be an economically viable and therapeutically superior alternative to the current generation of antimicrobial, antiviral and chemotherapeutic agents.

Publications

Parsley, N; Smythers, A; Hicks, L. Implementation of microfluidics for antimicrobial susceptibility assays: issues and optimization requirements. Frontiers in Cellular and Infection Microbiology. 2020, 10, 547177.  

Parsley, N; Williams, O; Hicks, L. Exploring the Diversity of Cysteine-Rich Natural Product Peptides via MS/MS Fingerprint Ions. Journal of the American Society for Mass Spectrometry. 2020, 31(9) (2020): 1833-1843.  

Moyer, T.B., Heil, L.R., Kirkpatrick, C.L., Goldfarb, D., Lefever, W.A., Parsley, N.C., Wommack, A.J. and Hicks, L.M. (2019) PepSAVI-MS Reveals a Proline-rich Antimicrobial Peptide in Amaranthus tricolor. Journal of Natural Products, 82, 2744-2753. 

Moyer, T; Parsley, N; Sadecki, P; Schug, W; Hicks, L. Leveraging orthogonal mass spectrometry based strategies for comprehensive sequencing and characterization of ribosomal antimicrobial peptide natural products. Natural Product Reports (2020).  

Parsley, N.C., Kirkpatrick, C.L., Crittenden, C.M., Rad, J.G., Hoskin, D.W., Brodbelt, J.S. and Hicks, L.M., (2018) PepSAVI-MS Reveals Anticancer and Antifungal Cycloviolacins in Viola odorata. Phytochemistry, 152, 61-70. 

Kirkpatrick, C.L., Parsley, N.C., Bartges, T.E., Wing, C.E., Kommineni, S., Kristich, C.J., Salzman, N.H., Patrie, S.M. and Hicks, L.M. (2018) Exploring Bioactive Peptides from Bacterial Secretomes Using PepSAVI-MS: Identification and Characterization of Bac-21 from Enterococcus faecalis pPD1. Microbial Biotechnology, 11, 943-951. 

Kirkpatrick, C.L., Parsley, N.C., Bartges, T.E., Cooke, M.E., Evans, W.S., Heil, L.R., Smith, T.J. and Hicks, L.M. (2018) Fungal Secretome Analysis via PepSAVI-MS: Identification of the Bioactive Peptide KP4 from Ustilago maydis. Journal of the American Society for Mass Spectrometry, 29, 859-865. 

Kirkpatrick, C.L., Broberg, C.A., McCool, E.N., Lee, W.J., Chao, A., McConnell, E.W., Pritchard, D.A., Hebert, M., Fleeman, R., Adams, J., Jamil, A., Madera, L., Stromstedt, A.A., Goransson, U., Liu, Y., Hoskin, D.W., Shaw, L.N. and Hicks, L.M. (2017) The “PepSAVI-MS” Pipeline for Natural Product Bioactive Peptide Discovery. Analytical Chemistry, 89, 1194-1201. 

Hicks Group Video