Abstract: The present relates to novel bioactive amphiphilic kanamycin compounds having the general formula of: where R may be a C4 to C20 branched or straight chained alkyl group or a substituted or unsubstituted aryl group. Also provided are methods of synthesizing and methods of using the compounds of the present invention. The compounds of the present invention are useful in treating and preventing various fungal and bacterial diseases.

Abstract: Antibody-free processes are disclosed that provide accurate quantification of a wide variety of low-abundance target analytes in complex samples. The processes can employ high-pressure, high-resolution chromatographic separations for analyte enrichment. Intelligent selection of target fractions may be performed via on-line Selected Reaction Monitoring (SRM) or off-line rapid screening of internal standards. Quantification may be performed on individual or multiplexed fractions. Applications include analyses of, e.g., very low abundance proteins or candidate biomarkers in plasma, cell, or tissue samples without the need for affinity-specific reagents.

Abstract: Various aspects relate to the use of C-1 gentamicin as an antibiotic effective for the treatment of a bacterial infection, a genetic disorder, or cancer in a subject.

Abstract: Vectors expressing kanA-kanB-kanK and other kanamycin production-related genes, Streptomyces species recombinant bacteria transformed with the vectors, a method of producing kanamycin antibiotics by the bacteria, and a new kanamycin compound produced by the bacterium are provided. With the use of the recombinant bacteria of the present invention, the direct fermentative biosynthesis of amikacin and tobramycin as semi-synthetic kanamycins is possible, and the yield of kanamycin B as a precursor of the semi-synthetic kanamycin is improved.

Abstract: The invention provides aqueous liquid pharmaceutical compositions comprising arbekacin and chloride ions. The compositions are well tolerable for use in a method for treatment or prevention of a disease of the upper or lower respiratory tract, wherein the composition is aerosolized and inhaled by the patient. Furthermore, the invention provides arbekacin hydrochloride.

Abstract: This invention relates in one aspect to non-natural desamino alkyl amino acid compounds, methods of making these compounds, and peptides containing these compounds. In one embodiment, the peptide is neurotensin (8-13) in which the N-terminus is an alpha-desamino, alpha-methyl-N,N-dimethyl-homolysine residue of the invention.

Abstract: In some aspects, the present invention provides aminoglycoside derivatives thereof that exhibit antibacterial activity. In some aspects, the aminoglycoside derivatives comprise compounds consisting of (a) an ammoglycoside group and (b) at least one hydrophobic carbamate and alkoxy group to the primary or secondary hydroxy position of the aminolvcoside group and salts thereof. Additionally, methods of treating and preventing bacterial infections using the aminoglycoside derivatives are also provided.

Abstract: The present invention provides albumin-binding probes capable of reversibly linking to short-lived amino-containing drugs and non-covalently associating with albumin in-vivo, thereby converting said drugs into inactive reactivable prodrugs having prolonged lifetime in-vivo. The invention further provides conjugates of said probes with amino-containing drugs, as well as pharmaceutical compositions and uses thereof.

Abstract: The present invention describes Photolabile Compounds methods for use of the compounds. The Photolabile Compounds have a photoreleasable ligand, which can be biologically active, and which is photoreleased from the compound upon exposure to light. In some embodiments, the Photolabile Compounds comprise a light antenna, such as a labeling molecule or an active derivative thereof. In one embodiment, the light is visible light, which is not detrimental to the viability of biological samples, such as cells and tissues, in which the released organic molecule is bioactive and can have a therapeutic effect. In another embodiment, the photoreleasable ligand can be a labeling molecule, such as a fluorescent molecule.

Abstract: Small molecule fluorescent probes for established drug targets such as nucleic acids including DNA and RNA has been developed and disclosed herein. These nucleic acid probes bind to multiple DNA and RNA structures, and to sites crucial for nucleic acid function, such as DNA and RNA major grooves. Displacement of the probes by other binders such as small molecule compounds and/or proteins illicits a fluorescence change in the probe that once detected and analyzed provide binding information of these other binders of interest. Similarly, changes in fluorescence upon binding of the probes to nucleic acid have been applied to screen nucleic acid of different sequence and conformation. The nucleic acid probes and method of uses disclosed herein are advantageously suitable for high-through put screening of libraries of small molecule compounds, proteins, and nucleic acids.

Abstract: The invention relates to anionic conjugates of glycosylated bacterial metabolites that may be used to mimic the structure and/or activity of the anionic bioactive molecules known as glycosaminoglycans (GAGs). The invention also relates to processes for the preparation of the conjugates. Such conjugates are useful in the prophylaxis and/or treatment of disease conditions and in particular chronic disease conditions such as inflammatory (including allergic) diseases, metastatic cancers and infection by pathogenic agents including bacteria, viruses or parasites.

Abstract: The present invention provides antimicrobial nanoparticle conjugates and an efficient method of preparing same. In particular, the invention relates to the preparation of antifungal nanoparticle conjugates comprising amphotericin B covalently immobilized to nanoparticles. The conjugates, and suspensions thereof, can be used to form antifungal coatings with particular application to medical devices and materials.

Abstract: The present invention relates to the prevention/treatment of ichthyosis vulgaris (IV), atopy and potentially other disorders associated with loss-of-function mutations in the filaggrin gene sequence. The prevention/therapy is based on the use of agents which enable the host's translational machinery to read through a nonsense mutation found in a mutant allele of the filaggrin gene.

Abstract: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I) or (II): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Q3, R1, R2, R3, R11 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

Abstract: Reagents and methods useful for the synthesis of conjugates comprising guanidinylated cyclic acetals are provided. Also provided are methods for increasing the cellular uptake of various therapeutic compounds and treatment modalities using these conjugates.

Abstract: The invention provides more effective methods of separating the components of gentamicin using a UV active protecting group suitable for use with HPLC.

Abstract: An antimicrobial composition comprising: a complex of a polysaccharide covalently bonded with an antibiotic. A medical device having an antimicrobial composition comprising: a complex of an oxidized regenerated cellulose covalently bonded with gentamicin.

Abstract: A method of treating chronic infection with B. cepacia complex (BCC) in a patient suffering from cystic fibrosis (CF) comprising administering a fluidosomal formulation of tobramycin to the patient.

Abstract: An aqueous or powder composition includes anti-gram-negative antibiotic or salt thereof being present at an amount ranging from about 100 mg/ml to about 200 mg/ml. Another aqueous or powder composition includes anti-gram-positive antibiotic or salt thereof being present at a concentration ranging from about 0.6 to about 0.9 of the water solubility limit, at 25° C. and 1.0 atmosphere, of the anti-gram-positive antibiotic or salt thereof. Other embodiments include unit doses, kits, and methods.

Abstract: Various aspects related to the preparation of congeners of the aminoglycosides gentamicin such as the congener C2 and using this compound or derivatives thereof and pharmaceutically active salts to treat diseases that involve genetic mutations which introduce a missense or premature stop codon into a gene. Still other aspects include treating human or animal patients with the gentamicin congener C2 and derivatives and pharmaceutical salt thereof to overcome, or to at least mitigate, the symptoms of disease and disorders such as some forms of Becker's or Duchenne muscular dystrophy, Hurler's Syndrome and Cystic Fibrosis that have as their etiology the presence of a premature stop codon in a gene whose proper expression is necessary for good health.

Abstract: The present invention provides a method for synthesizing 1-(acyloxy)-alkyl derivatives from 1-acyl-alkyl derivatives, which typically proceeds stereospecifically, in high yield, does not require the use of activated intermediates and/or toxic compounds and is readily amendable to scale-up. The current invention also provides 1-acyl-alkyl derivatives of known drug components and methods for synthesizing these 1-acyl-alkyl derivatives.

Abstract: The present invention provides a method for the measurement of an analyte in biological samples whereby an uncompetitive inhibitor is coupled to a ligand and utilized in a homogeneous assay. The analyte can be a drug or drug derivative, hormone, polypeptide, or oligonucleotide. The present invention also provides novel compounds, assay reagents and packaged kits useful for performing such measurements.

Abstract: Aminoglycoside-polyamines are disclosed along with methods of use thereof in displacement chromatography and as DNA-binding ligands. The aminoglycoside-polyamines are derivatives of carbohydrates, such as sugars, amino sugars, deoxysugars, glycosides, nucleosides and their substituted counterparts. The subject polyamines possess a group in place of at least one hydrogen atom of at least one hydroxyl group of the carbohydrate compound. In these compounds R1 is an alkyl group or an azaalkyl group, and R2 is a primary or secondary amino group.

Abstract: The invention provides a method of potentiating the activity of antibacterial agents that act on bacterial cell walls, comprising the step of administering to a subject an antibacterial agent and an aminoglycoside to attain a peak concentration of at least 4 mg/l of aminoglycoside and thereafter maintaining the aminoglycoside at a concentration of up to 4 mg/l for at least 1 hour. Compositions comprising an antibacterial agent and an aminoglycoside for efficacious treatment of bacterial infection are also provided.

Abstract: Conjugates of a saccharide and an acetamidino- or guanidino-compound, of the formula: wherein A is CH3 or NH2; X is a linear or branched C1-C8 alkyl chain optionally containing hydroxy, amino and/or oxo groups; n is an integer from 1 to 6, and Sac is the residue of a mono-or oligo-saccharide, provided that when A is NH2 and X is -(CH2)3—CH(NH2)—C(=O)-, the monosaccharide residue is not substituted at the position 1, and n is an integer from 2 to 6 when Sac is the residue of an oligosaccharide, are useful as antiviral, particularly as antiretroviral, agents, and can be used either alone or together with other compounds used in AIDS treatment such as AZT and/or protease inhibitors, for the treatment of HIV-infection, AIDS and manifestations of AIDS such as Kaposi sarcoma.

Abstract: Protein targets for disease intervention through inhibition of nucleic acid metabolism are disclosed. Novel polypeptides for one such target, DNA-dependent ATPase A, and novel polynucleotides encoding DNA-dependent ATPase A are disclosed. Phosphoaminoglycoside compounds which act on such protein targets to inhibit nucleic acid metabolism. In addition, screening assays for identifying compounds that inhibit nucleic acid-dependent ATPase activity, including, but not limited to, DNA-dependent ATPase A, are disclosed. Such compounds are useful in the treatment of diseases, including but not limited to cancer and infectious disease, through disruption of nucleic acid metabolism and induction of apoptosis. Moreover, methods for prevention and treatment of diseases including, but not limited to cancer and infectious disease are disclosed.

Abstract: The invention provides a method of potentiating the activity of antibacterial agents that act on bacterial cell walls, comprising the step of administering to a subject an antibacterial agent and an aminoglycoside to attain a peak concentration of at least 4 mg/l of aminoglycoside and thereafter maintaining the aminoglycoside at a concentration of up to 4 mg/l for at least 1 hour. Compositions comprising an antibacterial agent and an aminoglycoside for efficacious treatment of bacterial infection are also provided.

Abstract: Transition metal complexes, referred to hereinafter as “metalloligands”, that catalyze the degradation of DNA and the cleavage of RNA at select sites are provided. In one embodiment, the metalloligand has the following structure: wherein R1 is an amino group, i.e. an NH, or an alkylamino group comprising 1 or 2 carbon atoms; wherein R2 is selected from the group consisting of an amino group, a hydroxyl group, i.e., O(H), an alkylamino group comprising 1 or 2 carbon atoms; and an alkylhydroxyl group comprising 1 or 2 carbon atoms; wherein J is a ligand which comprises at least one carbon-containing five-membered or six-membered ring structure; and wherein M is a transition metal ion which is bound via coordinate bonds to R1 and R2.

Abstract: The present invention is directed to analogs of aminoglycoside compounds of the class having a glycosylated 2-deoxystreptamine (2-DOS) ring as well as their preparation and use as prophylactic or therapeutics against microbial infection. Compounds of the invention comprises at least one aryl, heteroaryl, substituted aryl or substituted heteroaryl group in place of a glycosyl group attached to the 2-deoxystreptamine ring.

Abstract: The invention provides a method of potentiating the activity of antibacterial agents that act on bacterial cell walls, comprising the step of administering to a subject an antibacterial agent and an aminoglycoside to attain a peak concentration of at least 4 mg/l of aminoglycoside and thereafter maintaining the aminoglycoside at a concentration of up to 4 mg/l for at least 1 hour. Compositions comprising an antibacterial agent and an aminoglycoside for efficacious treatement of bacterial infection are also provided.