Abstract: This disclosure relates to intranasal administration of conjugates comprising guanidinylated aminoglycosides (“guanidinoglycosides”) and a polypeptide (e.g., an enzyme, antibody, or polypeptide growth factor). For example, such administration methods are useful for delivering a polypeptide to the brain and/or cerebrospinal fluid. Such methods are useful for treating a lysosomal storage disease through intranasal administration of a conjugate comprising one or more guanidinoglycosides and an enzyme useful for treating a lysosomal storage disease.

Abstract: The present invention relates to an endoprosthesis with a drug coating comprising or consisting of at least one antibiotic agent and at least one further substance having the following general

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: 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: 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: Hydrophobically enhanced aminoglycosides have been prepared and shown to be effective antibacterial agents. These agents may be used in the treatment or prevention of various bacterial infections. Methods of preparing these agents also permit facile synthetic access. Formula (I).

Abstract: The invention relates to drug development and synthetic chemistry, in particular to the manufacture of biologically active compounds based on naturally occurring molecules. It also relates to novel biologically active compounds, for example aminoglycoside antibiotics, in a substantially pure regioisomeric form.

Abstract: Provided herein are antimicrobial conjugates of two antibiotic agents, exhibiting improved activity also against resistant bacteria, compared to each of the agents separately or their mixture, and having substantially no resistance emerged thereagainst, as well as processes for preparation the same, compositions containing the same, and uses thereof in medical treatments against pathogenic microorganisms. The disclosed antimicrobial conjugates are composed of aminoglycosides and non-ribosomal active antibiotics. Some of the antimicrobial conjugates are prepared via “click” chemistry.

Abstract: The present invention relates to immobilized biologically active entities that retain a significant biological activity following manipulation. The invention also comprises a medical substrate comprising a heparin entity bound onto a substrate via at least one heparin molecule, wherein said bound heparin entity is heparinase-1 sensitive.

Abstract: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Q5, R1, R2, R3, Z1 and Z2 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: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Z1, Z2, Z3, Z4, R1, R2 and R3 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: The present disclosure defines a method for identifying and/or treating risk and/or occurrence of cardiac defect. As is shown herein, microbiomes are reproducibly and detectably associated with cardiac defect risk factors and changes to the microbiome can directly alter cardiac defect risk. The present disclosure demonstrates that microbial signatures can be used to characterize components of microbiomes that associate with altered risk or occurrence of cardiac defects and to identify treatments to reduce risk or severity of cardiac defects.

Abstract: Guanadinylated aminoglycoside-lipid conjugates are prepared. Such conjugates may comprise an aminoglycoside such as an aminoglyucoside antibiotic like neomycin or kanamycin, at least one guanidino group attached to a primary or secondary carbon atom of the aminoglyucoside group and at least one lipid group attached through a bond or a linker to a branched carbon atom of the aminoglycoside. These conjugates exhibit improve antibacterial activity and may be used in conjunction with another antibiotic.

Abstract: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2 and R3 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: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2 and R3 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: 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): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, wherein Q1 and Q2 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: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2, R3, Z1 and Z2 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: Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, R1, R2 and R3 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: Provided herein are antimicrobial conjugates of two antibiotic agents, exhibiting improved activity also against resistant bacteria, compared to each of the agents separately or their mixture, and having substantially no resistance emerged thereagainst, as well as processes for preparation the same, compositions containing the same, and uses thereof in medical treatments against pathogenic microorganisms. The disclosed antimicrobial conjugates are composed of aminoglycosides and non-ribosomal active antibiotics. Some of the antimicrobial conjugates are prepared via “click” chemistry.

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 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 dimerization of HIV RNA is a key step in the virus replication cycle. Based on RNA DIS crystal structures, a novel kind of compounds, dimeric or not, based on neamine was designed and synthesized. Biological studies showed that such compounds bind and interfere with the targeted RNA sequence, opening a new anti-HIV approach. The crystal structures and bio-chemical experiments showed that the DIS of HIV-1 genomic RNA is a target for new anti-HIV drugs and that those drugs could be derived from aminoglycosides. The results revealed that binding of aminoglycosides to the DIS is specific regarding both the aminoglycoside family and the RNA subtype.

Abstract: The present invention is directed to analogs of paromomycin having a variety of chemical functional groups attached at the 2?-O-position as well as their preparation and use as prophylactic or therapeutics against microbial infection.

Abstract: A novel group of aminoglycosides which share some structural features of currently available aminoglycosides with regard to the backbone, while also having significant structural differences, is disclosed. The similarity enables these aminoglycosides to be highly potent and effective antibiotics, while the significant differences enable these aminoglycosides to reduce or even block antibiotic resistance. The aminoglycosides of the present invention are suitable for inhibition of antrax lethal factor, hence are suitable for use as a cure for anthrax.

Abstract: The present invention relates to aminoglycoside compounds having antibiotic activity. Moreover, the present invention relates to L-aminoglycoside compounds and diastereomers thereof which posses antibiotic activity and are not susceptible to development of resistant bacterial strains. The present invention also relates to methods of treatment and pharmaceutical compositions that utilize or comprise one or more of aminoglycoside compounds provided by the invention.

Abstract: Novel amino-modified polysaccharides are provided. The amino-modified polysaccharides have one or more amino groups, each being linked to one or more arginine residues.

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: Provided are reagents and methods useful for the synthesis of guanidinylated compounds. Also provided are methods for assaying molecules, including guanidinylated molecules that modulate viral infection and replication.

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: 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 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: Provided are reagents and methods useful for the synthesis of guanidinylated compounds. Also provided are methods for assaying molecules, including guanidinylated molecules that modulate viral infection and replication.

Abstract: The present invention is directed to using neomycin or an analogue thereof as an therapeutic agent to treat angiogenesis-related diseases, which are characterized by excessive, undesired or inappropriate angiogenesis or proliferation of endothelial cells. The present invention is also directed to pharmaceutical compositions comprising (a) neomycin or an analogue and, optionally, (b) another anti-angiogenic agent or an anti-neoplastic agent. The present invention is further directed to a method for screening neomycin analogues having anti-angiogenic activity. A preferred embodiment of the invention relates to using neomycin to treat subjects having such diseases.

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.