The University of Texas System

Mississippi State University

Oragenics, Inc.

Sano Chemicals

James Leif Smith

Shien Lu

Jeffrey Daniel Hillman

Ganyu Gu

Akshaya Ravichandran

Frank Austin

Shawanda R Wilson-Stanford

Jerome Escano

Stephen B Pruett

Ravi Shankar Orugunty

Mengxin Geng

Ravichandran Akshaya

Ravi Orugunty

Steven Laihing

Shein Lu

Ravi S Orugunty

The subject invention pertains to methods for producing novel occidiofungin analogues lacking xylose (OF-Δxyl analogue). OF-Δxyl analogues can contain aldehyde, amine, triazole, or hydrazones. The aldehyde, amine, triazole or hydrazone containing analogues of OF-Δxyl can be further modified by substitution with additional functional groups. Various OF-Δxyl analogues described herein have reduced inflammation and toxicity and superior pharmacological properties compared to the natural occidiofungins. Accordingly, certain embodiments of the invention provide methods of treating or preventing fungal infections by administering to the subjects in need thereof the OF-Δxyl analogues described herein.

Synthesis of novel xylose free occidiofungin analogues and methods of using them

Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar activity. This invention is directed to compositions enriched for particular occidiofungin diastereomers/conformers, methods of making compositions enriched for particular diastereomers/conformers and microorganisms suitable for producing enriched compositions of particular diastereomers/conformers. Methods of treating fungal infections or plants infected by fungi are also provided.

Engineering the production of a conformational variant of occidiofungin that has enhanced inhibitory activity against fungal species

The subject invention pertains to a modified lantibiotic containing an intact cysteine at the C-terminus, particularly, a cysteine that is not decarboxylated and that contains a free carboxyl group. Derivatives of the modified lantibiotic comprising a moiety conjugated to the carboxyl group of the terminal cysteine are also provided. A bacterium that produces a modified lantibiotic having an intact cysteine at the C-terminus are also provided, wherein the bacterium is genetically modified to inactivate a gene that encodes a decarboxylase enzyme that decarboxylates the cysteine at the C-terminus of a precursor lantibiotic. Methods of producing a modified lantibiotic having an intact cysteine at the C-terminus by culturing a bacterium that synthesizes the modified lantibiotic and purifying the lantibiotic are also provided. Mutants of lantibiotics, particularly, mutacin 1140 having higher anti-bacterial activity or higher bacterial expression compared to mutacin 1140 are also provided.

Modified lantibiotics and methods of making and using the modified lantibiotics

Disclosed are occidiofungin formulations and uses thereof for the treatment of proliferative disorders, such as cancer. Methods of producing the disclosed occidiofungin formulations are also provided. Further, methods of treating a subject with the formulations are provided. In some embodiments, the formulations include occidiofungin and one or more cyclodextrins. The formulations may optionally further comprise an additional chemotherapeutic agent for treating the proliferative disease, lipid vesicles, and/or aqueous solvents (including pharmaceutically acceptable buffers and/or exceipients).

Occidiofungin formations and uses thereof

The present invention is directed to novel antifungal glycopeptide compounds and salts thereof produced by a strain ofuseful for preventing or treating fungal infection or disease in animals and plants and the bacterial strain that produces the compounds.

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The invention provides improvements of lantibiotics useful for reducing the numbers of microbes or the reproduction of microbes in or on subjects or objects. One embodiment of the invention provides variants of antibiotics wherein the amino acid at position (1) is changed to Ile or Gly, the amino acid at position (4) is changed to an Ala, the amino acid at position (4) is removed, the amino acid at position (5) is changed to an Ala, or wherein, as in the case of MU1140, the amino acid at position (13) is Arg, the Arg at position (13) is substituted with Asp, or combinations of two or more these changes or a pharmaceutically acceptable salt thereof.

Variants of the lantibiotic MU1140 and other lantibiotics with improved pharmacological properties and structural features

The invention provides recombinantstrains that can be used to improve oral health. An embodiment of the invention provides a method of reducing the incidence or severity of dental caries in a dental caries-susceptible host comprising administering orally to the host an isolated recombinantstrain of the invention in an amount effective for replacement of dental caries-causinghost strains in the oral cavity of the host. The isolated recombinantstrain 10 can be contained in a mouthwash, toothpaste, chewing gum, floss, chewable tablet, food, or beverage.

Replacement therapy for dental caries

The present invention provides methods for adding functional hydrophobic, charge, polar, and other structural groups on antimicrobial compounds for enhancing the physicochemical properties of the antimicrobial compounds, thereby creating novel antimicrobial analogs with enhanced functions.

Functional enhancement of antimicrobials

The present invention provides a method of synthesizing an intramolecularly bridged polypeptide comprising at least one intramolecular bridge. The present invention further provides a method of synthesizing an intramolecularly bridged polypeptide comprising two intramolecular bridges, wherein the two intramolecular bridges form two overlapping ring, two rings in series, or two embedded rings. The present invention also provides methods for synthesizing lantibiotics, including Nisin A. Additionally, the invention provides intramolecularly bridged polypeptides synthesized by the methods disclosed herein and differentially protected orthogonal lanthionines.

Growing community of inventors

College Station, TX, United States of America

James Leif Smith