The total synthesis and evaluation of key analogs of vancomycin containing single atom changes in the binding pocket are disclosed as well as their peripherally modified, N-(hydrophobe-substituted) derivatives exemplified by a N-4-(4-chlorob-phenyl)-methyl derivative and their pharmaceutically acceptable salts are disclosed. Their evaluation indicates the combined pocket and peripherally modified analogs exhibit a remarkable spectrum of antimicrobial activity and truly impressive potencies against both vancomycin-sensitive and -resistant bacteria, and likely benefit from two independent and synergistic mechanisms of action. A pharmaceutical composition containing a contemplated compound or its pharmaceutically acceptable salt is disclosed, as is a method of treating a bacterial infection in a mammal by administering an antibacterial amount of a contemplated compound or its salt as above to an infected mammal in need of treatment.

Drug substance preparations of oritavancin having high purity are disclosed, along with pharmaceutical compositions comprising such oritavancin drug substance preparations, and drug products or dosage forms comprising such pharmaceutical compositions.

The present invention relates to a method for preparing a sialic acid derivative characterized by performing both of a process for preparing CMP-N-acetylneuraminic acid using N-acetyl-D-glucosamine and a process for preparing the sialic acid (neuraminic acid) derivative that combines a sialic acid with a galactose derivative or a lactose derivative, together, in one reactor. According to the method for preparing a sialic acid derivative of the present invention, expensive cytidine 5-monophosphate (CMP) is capable of being recycled in a reactor, such that an amount of the CMP introduced into the reactor may be reduced, and the sialic acid derivative is capable of being prepared at a significantly high efficiency by using cheap N-acetyl-D-glucosamine, and pyruvate as substrates.

Microspheres are produced by contacting a solution of a macromolecule or small molecule in a solvent with an antisolvent and a counterion, and chilling the solution. The microspheres are useful for preparing pharmaceuticals, nutraceuticals, cosmetic products and the like of defined dimensions.

This invention is directed to a novel method of treating an individual suffering from a bacterial infection, such as bacterial infections of various tissues or organs of an individual. In general, the method of treatment involves administering to an individual a pharmaceutical formulation that comprises a liposome-encapsulated antimicrobial agent, wherein polyethylene glycol (PEG) molecules are covalently attached to the surface of the liposomes.

The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.

Provided herein are compounds that can exhibit activity as biofilm modulating agents (e.g., activity as biofilm inhibitors and/or activity as biofilm dispersal agents). The compounds can exhibit potent activity against Gram positive biofilms. The compounds can also exhibit activity against Gram negative biofilms. In some cases, the compounds can exhibit both biofilm modulation properties and antimicrobial activity. Compositions comprising these compounds, as well as methods of using thereof, are also described. For example, the compounds described herein can be used in human and animal health (e.g., for the treatment of infection), agriculture, marine coatings, and other coating applications related to prevention of biofilm (e.g., dental, medical, etc.).

Bacterial infections evading the current antibiotic arsenal warrant new treatment options. The mainstay treatment for Clostridium difficile infections involves administration of the broad-spectrum antibiotic vancomycin, which also depletes the gut microbiome and its natural defenses. This leads to recurrent C. difficile infections in 20-30% of patients. Alternative treatment options are limited, triggering a perpetual cycle of relapse and recovery that may eventually lead to death. Keratinicyclin B represents a glycopeptide antibiotic chemotype with a mechanism of action that is selective for Clostridia. When combined, vancomycin (or other glycopeptide antibiotic) and keratinicyclin B interact synergistically to inhibit the growth of C. difficile at concentrations far lower than their respective minimal inhibitory concentrations. Such a combination therapy could allow for targeted colonization clearance at low antibiotic doses, thereby minimizing toxicity and reducing the likelihood of relapse.

The present disclosure provides novel vancomycin derivatives that act as antimicrobials against Gram-negative bacteria. The compounds of the present disclosure are believed to be useful for the treatment of diseases caused by antimicrobial resistant bacteria, including Acinetobacter baumannii and Escherichia coli.