Abstract: Provided are compounds, the use of the said compounds in treatment, for example treatment of microbial infections, particularly by Gram negative bacteria. The compounds are polymyxin-based and are represented by the formula (I): and pharmaceutically acceptable salts thereof, where X is —NHC(O)—, —C(O)—, —OC(O)—, —CH2— or —SO2—; R5 represents C0-12 alkyl(C4-6 heterocyclyl), or C2-12 alkyl or C0-12 alkyl(C3-8 cycloalkylyl). and the alkyl or cycloalkylyl bears one, two or three hydroxyl groups, or a —NR6R7 group, or one —NR6R7 group and one or two hydroxyl groups; and R1 to R4 and R6 to R8 are as defined in the description.

Abstract: A liquid colloidal pharmaceutical formulation of a type B lantibiotic for infusion or direct injection is described, the formulation being clear of visual particulates and comprising a type B lantibiotic or a salt thereof, an isotonic aqueous solution comprising a sugar alcohol and optionally a buffer.

Abstract: Described are lantibiotic-based compounds, pharmaceutical compositions comprising the same and use of the compounds and said compositions, for the treatment of microbial infection, for example Clostridium difficile or Micrococcus luteus infection. The lantibiotic-based compounds have antimicrobial activity and in comparison to one or more of actagardine, actagardine B, deoxyactagardine B and deoxyactagardine have retained activity or improved activity.

Abstract: Provided are compounds, the use of the said compounds in treatment, for example treatment of microbial infections, particularly by Gram negative bacteria. The compounds are polymyxin-based and are represented by the formula (I): and pharmaceutically acceptable salts thereof, where X is —NHC(O)—, —C(O)—, —OC(O)—, —CH2— or —SO2—; R5 represents C0-12 alkyl(C4-6 heterocyclyl), or C2-12 alkyl or C0-12 alkyl(C3-8 cycloalkyl). and the alkyl or cycloalkyl bears one, two or three hydroxyl groups, or a —NR6R7 group, or one —NR6R7 group and one or two hydroxyl groups; and R1 to R4 and R6 to R8 are as defined in the description.

Abstract: The present invention pertains generally to certain compounds of the deoxyactagardine A and B type. Such compounds are suitable for use in the treatment of microbial infections, for example Clostridium infection, such as C. perfringens, C. difficile, C. tetani, and/or C. botulinum, in particular C. difficile, especially infection of the colon and/or lower intestines and diarrhea associated with the microbial infection.

Abstract: Compounds of formula (IV) and pharmaceutical compositions comprising the same are described, wherein X1 and X2, R3, L, Ar1, p and Z have the values disclosed herein.

Abstract: A method for the treatment or prophylaxis of a microbial infection of the lower intestine or colon in a subject is described, wherein the method comprises administration to the subject of a type-B lantibiotic, wherein the type-B lantibiotic may include compounds selected from the group consisting of mersacidin, actagardine, plantaricin, planosporicin, ruminococcin, antibiotic 10789, michiganin and haloduracin, and derivatives and variants thereof.

Abstract: Described is a pharmaceutical formulation of a capsule for oral delivery of a type B lantibiotic to the stomach comprising a hard gelatine, HPMC or starch capsule, and a type B lantibiotic of formula (I): wherein X is —NH(CH2)qNH2 and q is an integer 2 to 12.

Abstract: Characterization of the biosynthetic gene cluster for the lantibiotic antibiotic actagardine, identification of a novel variant of actagardine and its biosynthetic cluster, and methods of production and use of actagardine, a novel actagardine variant, herein referred to as actagardine B, and variants of both of these produced according to this invention, utilizing genes from the characterized biosynthetic gene clusters, is described.

Abstract: Described is a A liquid colloidal pharmaceutical formulation of a type B lantibiotic for infusion or direct injection comprising a type B lantibiotic or a salt thereof, an isotonic aqueous solution comprising a sugar alcohol such as glycerol and/or a saccharide and optionally a buffer, wherein said final formulation for infusion or direct injection is clear of visual particulates.

Abstract: The present invention provides actagardine, actagradine B and deoxy actagardine B derivatives of formula (I), wherein: X1 denotes that the residue is Leu; Val; or Ile; X2 denotes that the residue is Leu; Val; or Ile; R1 represents an alkyl or heteroalkyl group, substituted by at least one hydroxyl substituent, and R2 represents hydrogen, or an alkyl or heteroalkyl group, optionally substituted by at least one hydroxyl substituent, or R1 and R2 taken together with the nitrogen atom represent a heterocyclic group having at least one hydroxyl substituent, wherein the heterocyclic group optionally further contains one or more heteroatoms; Z is an amino acid residue, —NR3R4, —NR5COR6, —NR5C(O)OR6; —NR5SOR6, NR5SO2R6; —NR5C(S)NR6R7, —NR5C(NR8)NR6R7, or —N?R9, where R3, R4, R5, R6, R7, R8 and R9 are independently hydrogen, or a group, optionally substituted, selected from alkyl, heteroalkyl, aryl, heteroaryl, aralkyl and heteroaralkyl, with the proviso that R9 is not hydrogen; and Y is —S— or —S(O)—.

Abstract: The present invention pertains generally to certain compounds of the deoxyactagardine A and B type. Such compounds are suitable for use in the treatment of microbial infections, for example Clostridium infection, such as C. perfringens, C. difficile, C. tetani, and/or C. botulinum, in particular C. difficile, especially infection of the colon and/or lower intestines and diarrhea associated with the microbial infection.

Abstract: This disclosure relates to the synthesis of the compound of formula (I) according to Scheme A below: in which R1, R2 and R3, which may be identical or different, represent, individually and independently, an alkyl group, characterized by an enzymatic hydrolysis reaction that involves placing the compound of formula (II) in contact with an enzyme that performs a chemoselective hydrolysis of only one of the two ester functions of the compound of formula (II) to obtain the compound of formula (I).

Abstract: A method for the treatment or prophylaxis of a microbial infection of the lower intestine or colon in a subject is described, wherein the method comprises administration to the subject of a type-B lantibiotic, wherein the type-B lantibiotic may include compounds selected from the group consisting of mersacidin, actagardine, plantaricin, planosporicin, ruminococcin, antibiotic 10789, michiganin and haloduracin, and derivatives and variants thereof.

Abstract: The present invention pertains generally to certain compounds of the deoxyactagardine A and B type. Such compounds are suitable for use in the treatment of microbial infections, for example Clostridium infection, such as C. perfringens, C. difficile, C. tetani, and/or C. botulinum, in particular C. difficile, especially infection of the colon and/or lower intestines and diarrhea associated with the microbial infection.

Abstract: This invention relates to characterisation of the biosynthetic gene cluster for the lantibiotic actagardine, identification of a novel variant of actagardine and its biosynthetic cluster, and methods of production and use of actagardine, a novel actagardine variant, herein referred to as actagardine B, and variants of both of these produced according to this invention, utilizing genes from the characterised biosynthetic gene clusters.

Abstract: The present disclosure relates to compounds of formula (II): pharmaceutical compositions comprising same and use of the compounds and compositions for the treatment of microbial infection, particularly Methicillin-resistant Staphylococcus aureus (MRSA) infection.

Abstract: Characterization of the biosynthetic gene cluster for the lantibiotic actagardine, identification of a novel variant of actagardine and its biosynthetic cluster, and methods of production and use of actagardine are described.

Abstract: The present invention pertains generally to certain compounds of the deoxyactagardine A and B type. Such compounds are suitable for use in the treatment of microbial infections, for example Clostridium infection, such as C. perfringens, C. difficile, C. tetani, and/or C. botulinum, in particular C. difficile, especially infection of the colon and/or lower intestines and diarrhea associated with the microbial infection.

Abstract: Characterization of the biosynthetic gene cluster for the lantibiotic actagardine, identification of a novel variant of actagardine and its biosynthetic cluster, and methods of production and use of actagardine are described.