Richard W. Scott
Fox Chase Cancer Center
Publications 74
#1Ibrahim AlkanfariH-Index: 1
#2Katie B. FreemanH-Index: 4
Last.Hydar AliH-Index: 30
view all 6 authors...
Host-defense peptides (HDPs) have an important therapeutic potential against microbial infections but their metabolic instability and cellular cytotoxicity have limited their utility. To overcome these limitations, we utilized five small-molecule, nonpeptide HDP mimetics (smHDPMs) and tested their effects on cytotoxicity, antimicrobial activity, and mast cell (MC) degranulation. None of the smHDPMs displayed cytotoxicity against mouse 3T3 fibroblasts or human transformed liver HepG2 cells. Howev...
#1Manunya Nuth (UPenn: University of Pennsylvania)H-Index: 7
#2Hancheng Guan (UPenn: University of Pennsylvania)H-Index: 8
Last.Robert P. Ricciardi (UPenn: University of Pennsylvania)H-Index: 22
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Abstract The smallpox virus (variola) remains a bioterrorism threat since a majority of the human population has never been vaccinated. In the event of an outbreak, at least two drugs against different targets of variola are critical to circumvent potential viral mutants that acquire resistance. Vaccinia virus (VACV) is the model virus used in the laboratory for studying smallpox. The VACV processivity factor D4 is an ideal therapeutic target since it is both essential and specific for poxvirus ...
#1Gill Diamond (UF: University of Florida)H-Index: 3
#2Lisa K. Ryan (UF: University of Florida)H-Index: 1
Last.Richard W. Scott (Fox Chase Cancer Center)H-Index: 39
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Systemic fungal infections are increasingly common, especially in immune compromised patients. Even with newly developed drugs, there remain issues of limited spectrum, side effects, and the development of resistance. Host defense peptides (HDPs) have been examined recently for their utility as therapeutic antifungals, especially due to the low levels of resistance that develop. Unfortunately, the peptides exhibit poor pharmacologic properties in vivo. We have demonstrated the potent activity of...
#2Lisa K. RyanH-Index: 13
Last.Gill DiamondH-Index: 34
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Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low mole...
1 CitationsSource
#1Lorenzo P. Menzel (UF: University of Florida)H-Index: 1
#2Hossain Mobaswar Chowdhury (UF: University of Florida)H-Index: 1
Last.Gill Diamond (UF: University of Florida)H-Index: 3
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Lethal systemic fungal infections of Candida species are increasingly common, especially in immune compromised patients. By in vitro screening of small molecule mimics of naturally occurring host defense peptides (HDP), we have identified several active antifungal molecules, which also exhibited potent activity in two mouse models of oral candidiasis. Here we show that one such compound, C4, exhibits a mechanism of action that is similar to the parent HDP upon which it was designed. Specifically...
10 CitationsSource
New infection treatments are urgently needed to combat the rising threat of multi-drug resistant bacteria. Despite early clinical set-backs attention has re-focused on host defense proteins (HDPs), as potential sources for new and effective antimicrobial treatments. HDPs appear to act at multiple targets and their repertoire includes disruptive membrane and intracellular activities against numerous types of pathogens as well as immune modulatory functions in the host. Importantly, these novel ac...
15 CitationsSource
#1Harvey Rubin (UPenn: University of Pennsylvania)H-Index: 37
#2Trevor Selwood (UPenn: University of Pennsylvania)H-Index: 12
Last.Allen B. Reitz (Fox Chase Cancer Center)H-Index: 31
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Abstract The Gram-negative bacterium Acinetobacter baumannii is an opportunistic pathogen in humans and infections are poorly treated by current therapy. Recent emergence of multi-drug resistant strains and the lack of new antibiotics demand an immediate action for development of new anti-Acinetobacter agents. To this end, oxidative phosphorylation (OxPhos) was identified as a novel target for drug discovery research. Consequently, a library of ∼10,000 compounds was screened using a membrane-bas...
3 CitationsSource
#1Bruk Mensa (UCSF: University of California, San Francisco)H-Index: 4
#2Gabriella L. Howell (UCSF: University of California, San Francisco)H-Index: 1
Last.William F. DeGrado (UCSF: University of California, San Francisco)H-Index: 95
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Brilacidin (PMX30063) has shown potent bactericidal activity against drug-resistant and -susceptible strains of multiple Gram-negative and Gram-positive pathogens. In this study, we demonstrate that brilacidin causes membrane depolarization in the Gram-positive bacterium Staphylococcus aureus, to an extent comparable to that caused by the lipopeptidic drug daptomycin. Transcriptional profiling of Staphylococcus aureus by deep sequencing shows that the global response to brilacidin treatment is w...
65 CitationsSource
#1Lisa K. Ryan (RU: Rutgers University)H-Index: 13
#2Katie B. FreemanH-Index: 4
Last.Gill Diamond (RU: Rutgers University)H-Index: 34
view all 10 authors...
There is a strong need for new broadly active antifungal agents for the treatment of oral candidiasis that not only are active against many species of Candida, including drug-resistant strains, but also evade microbial countermeasures which may lead to resistance. Host defense peptides (HDPs) can provide a foundation for the development of such agents. Toward this end, we have developed fully synthetic, small-molecule, nonpeptide mimetics of the HDPs that improve safety and other pharmaceutical ...
16 CitationsSource
#1William F. DeGradoH-Index: 95
Last.Richard W. ScottH-Index: 39
view all 11 authors...
A series of self-associating foldamers have been designed as heparin reversal agents, as antidotes to prevent bleeding due to this potent antithrombotic agent. The foldamers have a repeating sequence of Lys-Sal, in which Sal is 5-amino-2-methoxy-benzoic ac