For over 23 years, my lab has worked on the chemistry and biology of modified HA, producing over 30 patents/patent applications and 136 peer-reviewed papers and chapters covering basic studies of HA chemistry and preclinical evaluation of HA-derived biomaterials in cell therapy, wound healing and surgical adhesion prevention. This HA technology has been translated into human and veterinary products through five start-up companies, and is highlighted in the following four publications:
G. D. Prestwich, “Clinical Biomaterials for Scar-Free Healing and Localized Delivery of Cells and Growth Factors,” Advances in Wound Care, 1, 394-399 (2010).
G. D. Prestwich, “Clinical Biomaterials Derived from Hyaluronic Acid for Use in Cell and Molecule Delivery in Regenerative Medicine,” J. Controlled Release, 155, 193-199 (2011).
J. Burdick, G. D. Prestwich, “Hyaluronic Acid Hydrogels for Biomedical Applications”, Advanced Materials 23, H41-H56 (2011).
G. D. Prestwich, I. Erickson, T. I. Zarembinski, M. West, and W. P. Tew. “The Translational Imperative: Making Cell Therapy Simple and Effective,” Acta Biomaterialia, 8, 4200-4207 (2012).
C. B. Highley, G. D. Prestwich, and J. A. Burdick, Recent advances in hyaluronic acid hydrogels for biomedical applications, Curr. Opin. Biotech, 40, 35-40 (2016).
Phosphoinositide and lysolipid affinity probes for cell signaling
Beginning in 1989, we began making affinity probes to study phosphoinositide and inositol polyphosphate binding proteins, leading to joint publications with some forty collaborators around the world. The popularity of the PIP analogs from my lab led to my co-founding of Echelon Biosciences, Inc in 1997, which is still a premiere source for PIP and IP reagents for cell signaling and drug discovery. In 2001, we expanded our academic studies to include synthesis of lysophosphatidic acid analogs as agonists and antagonists for receptors and enzymes.
G.D. Prestwich, J.F. Marecek, R.J. Mourey, A.B. Theibert, C.D. Ferris, S.K. Danoff, and S.H. Snyder, “Tethered IP3. Synthesis and Biochemical Applications of the 1O(3 Amino-propyl) Ester of Inositol (1,4,5) Trisphosphate,” J. Am. Chem. Soc., 113, 18221825 (1991).
V.A. Estevez and G.D. Prestwich, “Synthesis of Chiral, P1 Tethered Inositol Tetrakisphosphate Affinity Labels via a Ferrier Rearrangement,” J. Am. Chem. Soc., 113, 98859887 (1991).
G. Dormán and G.D. Prestwich, “Benzophenone Photophores in Biochemistry,” Biochemistry, 33, 56615673 (1994).
G.D. Prestwich “Touching All the Bases: Inositol Polyphosphate and Phosphoinositide Affinity Probes from Glucose,” Acc. Chem. Res., 29, 503-513 (1996).
G. Dorman, H.Nakamura, A. Pulsipher, and G. D. Prestwich, The life of pi star: Exploring the exciting and forbidden worlds of the benzophenone photophore, Chem. Rev., 116 (24), 15284–15398; doi 10.1021/acs/chemrev.6b00342 (2016).
Translational medicine of sulfated glycosaminoglycans
Since 2008, we have developed semisynthetic glycosaminoglycan ethers (SAGEs) as therapeutic agents for preventing and/or treating inflammatory pathophysiologies involving the innate immune system. Three primary indications include: (a) treatments for periodontal disease/gingivitis, (b) intravesical installation for interstitial cystitis/painful bladder syndrome, and oral treatments for radiation-induced oral mucositis.
J. Zhang, X. Xu, N. V. Rao, B. Argyle, L. McCoard, W. J. Rusho, T. P. Kennedy, G. D. Prestwich, and G. Krueger, “Novel Sulfated Polysaccharides Disrupt RAGE Ligation and Inhibit Cutaneous Inflammation in a Mouse Model of Rosacea”, PLOS One 6 (2), e16658 (2011)
S. Oottamasathien, W. Jia, L. McC. Roundy, J. Zhang, X. Ye,, A. C. Hill, J. Savage, W. Y. Lee, A. M Hannon, S. Milner, and G. D. Prestwich, “Physiologic relevance of LL-37 induced bladder inflammation and mast cells,” J. Urol., 190, 1596-1602 (2013).
W. Y. Lee, J. R. Savage, J. Zhang, W. Jia, S. Oottamasathien, and G. D. Prestwich, Prevention of anti-microbial peptide LL-37 induced ATP release in the urinary bladder by a modified glycosaminoglycan, PLoS ONE, 8(10) e77854 (2013).
J. Alt, X. Qin, A. Pulsipher, Q. Orb, R. R. Orlandi, J. Zhang, A. Schults, W. Jia, A.P. Presson, G. D. Prestwich, and S. Oottomasathien, Topical cathelicidin (LL-37), an innate immune peptide, induces acute olfactory inflammation in a mouse model, Int. Forum Allergy Rhinitis, 5 (12), 1141-1150 (2015)
J. Savage, A. Pulsipher, N. V. Rao, T. P. Kennedy, G. D. Prestwich, M. E. Ryan, and W. Y. Lee, A modified glycosaminoglycan, GM-0111, inhibits molecular signaling involved in periodontitis, PLoS ONE, 11 (6) e0157310 (2016).
A. Pulsipher, X. Qin, A. Thomas, G. D. Prestwich, S. Oottamasathien and J. Alt, Prevention of sinonasal inflammation by a synthetic glycosaminoglycan, Int. Forum Allergy & Rhinitis, 7 (2), 177-184 (2017).
W. Jia, A.J. Schults, X. Ye, J. A. Alt, G. D. Prestwich, and S. Oottamasthien, Bladder pain in LL-37 interstitial cystitis and painful bladder syndrome model, Am. J. Clin. Exp. Urol., 5 (2): 10-17 (2017)
M. M. Jensen, W. Jia, K.Isaccson, A. Schults, J.Cappello, G. D. Prestwich, S. Oottamasathien, and H. Ghandehari, Silk-elastinlike protein polymers enhance the efficacy of a therapeutic glycosaminoglycan for prophylactic treatment of radiation-induced proctitis, J. Controlled Rel., http://dx.doi.org/10.1016/j.jconrel.2017.02.025 (2017).
J. Paderi, G. Prestwich, A. Panitch, T. Boone, and K. Stuart, Glycan Therapeutics: Resurrecting an Almost Pharma-Forgotten Drug Class, Adv. Therapeutics, DOI:10.1002/adtp.201800082 (2018).
J. A. Alt, A. Pulsipher, B. M. Davis, W. Y. Lee, J. R. Savage, T. P. Kennedy, G. D. Prestwich, A synthetic glycosaminoglycan reduces sinonasal inflammation in a murine model of chronic rhinosinusitis, PLOS ONE, 13 (9):e0204609 (2018)
Natural products of insect chemical communication
From my postdoctoral work in East Africa and 6 years at Stony Brook, I published >50 papers in this area. I wrote and photographed an article in the April 1978 National Geographic; more scientific highlights include:
J. Meinwald, G.D. Prestwich, K. Nakanishi, and I. Kubo, “Chemical Ecology: Studies from East Africa,” Science, 199, 11671173 (1978).
S.G. Spanton and G.D. Prestwich, “Chemical Self-Defense by Termite Workers: Prevention of Autotoxication in Two Rhinotermitids,” Science, 214, 13631365 (1981).
G.D. Prestwich, “From Tetracycles to Macrocycles: Chemical Diversity in the Defense Secretions of Nasute Termites,” Tetrahedron, Symposium-in-Print, 38, 1911-1919 (1982).
G.D. Prestwich, “The Chemical Defenses of Termites,” Scientific American, pp. 78-87 (August 1983).
Insect hormone, pheromone, and steroid biochemistry
From 1982 – 1990, I changed from natural products chemistry to studies of insect biochemistry, developing affinity probes, e.g., photoaffinity reagents and irreversible enzyme inhibitors, to characterize the proteins involved in binding and metabolizing insect steroids, insect pheromones, and insect juvenile hormones. Selected representative summary papers include the following:
G.D. Prestwich, A.K. Gayen, S. Phirwa, and T.B. Kline, “29-Fluorophytosterols: Novel Proinsecticides Which Cause Death by Dealkylation,” Bio/Technology, 1, 6265 (1983).
G.D. Prestwich, “Chemistry of Pheromone and Hormone Metabolism in Insects,” Science, 237, 999-1006 (1987).
R.G. Vogt, G.D. Prestwich, and L.M. Riddiford, “Sex Pheromone Receptor Proteins: Visualization Using a Radiolabeled Photoaffinity Analog,” J. Biol. Chem., 263, 39523959 (1988).
S.R. Palli, E. Osir, M.F. Boehm, W.-s. Eng, M. Edwards, P. Kulcsár, I. Ujváry, K. Hiruma, G.D. Prestwich, and L.M. Riddiford, “Juvenile Hormone Receptors in Larval Epidermis: Identification by Photoaffinity Labeling,” Proc. Natl. Acad. Sci. USA, 87, 796-800 (1990).
G.D. Prestwich, “Photoaffinity Labeling and Biochemical Characterization of Binding Proteins for Pheromones, Juvenile Hormones, and Peptides,” Insect Biochem., 21, 2740 (1991).
Modulation of mammalian cholesterol biogenesis
From 1984 – 1994, I expanded my interest in insect isoprenoids and enzymes processing them to include mammalian isoprenoids, particularly sterols. We obtained corporate, NSF, and NIH support to develop affinity probes and enzyme inhibitors for sterol biogenesis and metabolism; several papers are highlighted:
S.E. Sen and G.D. Prestwich, “Squalene Analogs Containing Isopropylidene Mimics as Potential Inhibitors of Pig Liver Squalene Epoxidase and Oxidosqualene Cyclase,” J. Med. Chem., 32, 2152-2158 (1989).
S.E. Sen and G.D. Prestwich, “Trisnorsqualene Cyclopropylamine: A Reversible, Tight Binding Inhibitor of Squalene Epoxidase,” J. Am. Chem. Soc., 111, 87618762 (1989).
I. Abe, M. Rohmer, and G.D. Prestwich, “Enzymatic Cyclization of Squalene and Oxidosqualene to Sterols and Triterpenes,” Chem. Rev., 93, 21892206 (1993).
I. Abe and G.D. Prestwich, “Active Site Mapping of AffinityLabeled Rat Oxidosqualene Cyclase,” J. Biol. Chem., 269, 802804 (1994).