Michael Ferracane

Chair, Associate Professor, Chemistry

Michael Ferracane

Areas of Expertise

  • Synthesis, NMR Spectroscopy, & Molecular Modeling
  • Peptide Structure & Function
  • Opioids & Opioid Receptors
  • O-Glycoprotease Enzymes


Ph.D., Organic Chemistry, University of Virginia, 2014


B.S., Chemistry & Biochemistry, University of Arizona, 2008

For the Media

Contact :
Media Relations


Chemistry, Hedco Hall
P: 909.307.7818
P: 909.748.8370
E: Michael_Ferracane@redlands.edu

Background & Research Interests

My research uses computational, synthetic, and spectroscopic methods to investigate the structure and behavior of peptides and the enzymes that degrade them. The goal of this work is to better understand the properties, activity, and therapeutic potential of these species.

In the first project, we study the structure and dynamic behavior of cyclic tetrapeptides to develop improved modulators of the opioid receptors for treatment of pain and/or addiction, two unmet medical needs. Cyclic tetrapeptides possess a unique molecular scaffold that imparts drug-like properties not typically seen in peptides, including (a) stability to degradation by peptidases/proteases as well as (b) oral bioavailability and (c) blood-brain barrier permeability. We use chemical synthesis, NMR spectroscopy, X-ray crystallography, and molecular modeling to better understand the structure and dynamic behavior of cyclic tetrapeptides to rationalize and improve their opioid activity.

In the second project, we study O-glycoprotease enzymes to better understand their structure, function, role in disease, and potential as drug targets. O-glycoproteases are produced by bacteria and are capable of degrading host O-glycoproteins, including those that comprise the protective mucus barrier lining the gastrointestinal tract. These enzymes are unusual in that they degrade glycosylated proteins but not their nonglycosylated analogs; the details of their unique substrate specificity are only now becoming clearer. We use molecular modeling to investigate O-glycoprotease structure and substrate recognition to better understand their specificity and potential as drug targets.

Both projects are highly collaborative, involving peers at institutions across the country. Research performed at Redlands is designed to produce meaningful science while providing practical research experience for undergraduate students interested in chemistry, biochemistry, medicine, or pharmacy.

Professional Experience

·      Visiting Assistant Professor, Department of Chemistry, University of California, Irvine

·     Assistant Professor, Department of Chemistry, University of Redlands

·      Post-Doctoral Associate, Department of Medicinal Chemistry, University of Florida


Courses Offered

  • CHEM 132 - General Chemistry II Lecture and Laboratory 
  • CHEM 231 - Organic Chemistry I Lecture and Lab
  • CHEM 232 - Organic Chemistry II Lecture and Lab
  • CHEM 320 - Biochemistry Lecture and Laboratory
  • CHEM 420 - Advanced Biochemistry


Shon, D.; Fernandez, D.; Riley, N.; Ferracane, M.; Bertozzi, C. Structure-guided mutagenesis of a mucin-selective metalloprotease from Akkermansia muciniphila alters substrate preferences. J. Biol. Chem. 2022, 298, 101917 https://doi.org/10.1016/j.jbc.2022.101917

Shon, D.; Kuo, A.; Ferracane, M.; Malaker, S. Classification, structural biology, and applications of mucin-targeting proteases. Biochem. J. 2021478, 1585-1603 https://doi.org/10.1042/BCJ20200607

Gisemba, S.; Ferracane, M.; Murray, T.; Aldrich, J. Conformational Constraint between Aromatic Residue Side Chains in the “Message” Sequence of the Peptide Arodyn Using Ring Closing Metathesis Results in a Potent and Selective Kappa Opioid Receptor Antagonist. J. Med. Chem. 202164, 3153-3164 https://doi.org/10.1021/acs.jmedchem.0c01984

Haurat, M.; Scott, N.; Di Venanzio, G.; Lopez, J.; Pluvinage, B.; Boraston, A.; Ferracane, M.; Feldman, M. The glycoprotease CpaA secreted by medically relevant Acinetobacter species targets multiple O-linked host glycoproteins. mBio 2020, 11, e02033-20 https://doi.org/10.1128/mBio.02033-20

Brice-Tutt, A.; Wilson, L.; Eans, S.; Stacy, H.; Simons, C.; Simpson, G.; Coleman, J.; Ferracane, M.; Aldrich, J.; McLaughlin, J. Multifunctional Opioid Receptor Agonism and Antagonism by a Novel Macrocyclic Tetrapeptide Prevents Reinstatement of Morphine-Seeking Behavior. Br. J. Pharmacol. 2020177, 4209-4222 https://doi.org/10.1111/bph.15165

Ferracane. M.; Brice-Tutt, A.; Coleman, J.; Simpson, G.; Wilson, L.; Eans, S.; Stacy, H.; Murray, T.; McLaughlin, J.; Aldrich, J. Design, Synthesis, and Characterization of the Macrocyclic Tetrapeptide cyclo[Pro-Sar-Phe-d-Phe]: a Mixed Opioid Receptor  Agonist-Antagonist Following Oral Administration. ACS Chem. Neurosci. 202011, 1324-1336 https://dx.doi.org/10.1021/acschemneuro.0c00086

Malaker, S.; Pedram, K.; Ferracane, M.; Bensing, B.; Krishnan, V.; Pett, C.; Yu, J.; Woods, E.; Kramer, J.; Westerlind, U.; Dorigo, O.; Bertozzi, C. The mucin-selective protease StcE enables molecular and functional analysis of human cancer-associated mucins. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 7278-7287 https://dx.doi.org/10.1073/pnas.1813020116

Malaker, S.; Ferracane, M.; Depontieu, F.; Zarling, A.; Shabanowitz, J.; Bai, D.; Engelhard, V.; Topalian, S.; Hunt, D. Identification and characterization of complex glycosylated peptides presented by the MHC class II processing pathway in melanoma. J. Prot. Res. 2017, 16, 228-237 http://dx.doi.org/10.1021/acs.jproteome.6b00496

Lefever, M.; Szabo, L.; Anglin, B.; Ferracane, M.; Hogan, J.; Cooney, L.; Polt, R. Glycosylation of α-amino acids by sugar acetate donors with InBr3. Minimally competent Lewis acids. Carb. Res. 2012, 351, 121-125 http://dx.doi.org/10.1016/j.carres.2012.01.008

Google Scholar  PubMed  ORCID 

Book Chapters

Malaker, S.; Ferracane, M. Mass Spectrometric Identification and Molecular Modeling of Glycopeptides Presented by MHC Class I and II Processing Pathways. In Immunoproteomics: Methods and Protocols, 2nd ed.; Fulton, K., Twine, S., Eds.; Methods in Molecular Biology; Humana: New York, 2019; 2024, pp 269-285 http://dx.doi.org/10.1007/978-1-4939-9597-4_17

Patent Applications

Aldrich, J.; Ferracane, M. Novel Macrocyclic Opioid Peptides. U.S. Patent Application 62/658,915, April 17, 2018


  • Molecular Modeling of Bacterial Mucinase Enzymes ($1,450) – 2022
    •          University of Redlands - Faculty Research Grant
  • LEAPS-MPS: Synthesis, Structural Analysis, and Characterization of Opioid Cyclic Tetrapeptides ($249,311) - 2022         
    •          National Science Foundation
  • Conformational Analysis and Molecular Modeling of Cyclic Tetrapeptides ($2,750) - 2019      
    •          University of Redlands - Faculty Research Grant





Awards & Honors

  • Outstanding Faculty Award for Research/Creative Activity - 2022                   
      • University of Redlands
  • Professor of the Year (Finalist) - 2019                                                                                       
      • Mortar Board - University of Redlands
  • Bert L. Schram Young Investigator Award (Finalist) - 2015                                     
      • American Peptide Society
  • Outstanding Graduate Teaching Assistant Award - 2012                                         
      • Graduate School of Arts & Sciences - University of Virginia
  • Alumni Award for Excellence in Undergraduate Research - 2007               
      • Department of Chemistry - University of Arizona

Professional Affiliations

·       American Chemical Society

·       American Peptide Society

·       Council on Undergraduate Research