Table 1.

Summarizes the four main classes of peptide antibiotics that target Lipid II: 1) glycopeptides, including the novel generation of lipoglycopeptides; 2) cyclic depsipeptide antibiotics; and 3) the lantibiotic group and 4) more recently, defensins

Class	Antibiotic or subclass	Stage of development	Described interaction with Lipid II	Refs
Glycopeptides	Vancomycin	Clinical use	Binds to terminal D-alanyl-D-alanine part of the pentapeptide side chain of MurNAc.	16
	Teicoplanin	Clinical use (Europe)	Similar to vancomycin (D-Ala-D-Ala domain of pentapeptide)	17
	Telavancin	Clinical use	Similar to vancomycin (D-Ala-D-Ala domain of pentapeptide)	18
	Dalbavancin	Clinical use	Similar to vancomycin (D-Ala-D-Ala domain of pentapeptide)	19
	Oritavancin	Clinical use	D-Ala-D-Ala domain of pentapeptide and additional motif at the lipid II stem peptide (crossbridge and the D-iso-glutamine in position 2)	20,21
	Mannopeptimycin	Preclinical	Unknown	22
Cyclic depsipeptide antibiotics	Katanosin B (lysobactin)	Preclinical	Complex formation with Lipid I, II and Lipid IIA (1:1)	23
	Plusbacin A3	Preclinical	Inhibition of PG chain extension by transglycosylation	24
	Ramoplanin	Phase III	Probably hydrogen bonds from the backbone NH groups of ramoplanin bind to the pyrophosphate moiety of Lipid II (2:1).	25
	Bacitracin		C55-PP	26
	Friulimicin		C55-PP	27
	Teixobactin	Preclinical	Probably hydrogen-bond interact-ions with the pyrophosphate moiety of Lipid II	28
Lantibiotics	Nisin	Preclinical	N-terminus lantinionine ring binds to pyrophosphate moiety via direct hydrogen bonding with polypeptide backbone of nisin. Also minor interactions with the first isoprene unit and the MurNAc sugar have been assumed.	29
Type A I	Subtilin	Preclinical	Similar to nisin (no structural differences in key positions)	30
(linear peptide)	Epidermin	Preclinical	Similar to nisin (no structural differences in key positions)	31
	Mutacin 1140	Preclinical	Similar to nisin (no structural differences in key positions)	32
Lantibiotics	Nukacin ISK-1	Preclinical	Based on structural similarity to mersacidin and positional significance of the amino acids in the region of ring A lipid II binding similar to mersacacidin is assumed	33
Type A II(both linear and globular)
Lacticin 481	Preclinical	Unknown	34
Lantibiotics	Mersacidin	Preclinical	Complexing the sugar phosphate group, electrostatic interactions and conformational changes are supposed to contribute to this interaction.	35
Type B(globular peptide)	Plantaricin C	Preclinical	Binding may be assigned to the same binding motif found in mersacidin but the molecular interaction differs from that between lipid II and mersacidin. An additional linking site might have been found as it contains a highly positively charged N terminus, which is missing in mersacidin.	36
Pediocin PD-1	Preclinical	Unknown	37
	Actagardine/gardimycin	Preclinical	Unknown	38
Two-component lantibiotics (synergistically acting type A I and B structures)	Lacticin 3147	Preclinical	A mersacidin like interaction between the A1 part of lacticin 3147 en lipid II is proposed.	39
Nonlantibiotic bacteriocins	Colicin M	Preclinical	Enzymatic cleavage of lipid II between the undecaprenyl and	40
			1-pyrophospho-MurNAc moiety
	Lactococcin 972	Preclinical	Unknown	41
Defensins and defensin- based compounds	Plectasin NZ2114	Preclinical	The pyrophosphate moiety forms hydrogen bonds to F2, G3 and C37 on plectasin. The D-gamma-glutamate of Lipid II forms a salt bridge with the N-terminus of plectasin and the side-chain of His18.	15
	Oryzeacin	Preclinical	Unknown
	Eurocin	Preclinical	Unknown
	Lucifensin	Preclinical	Unknown
	Gallicin	Preclinical	Unknown
	HNP-1	Preclinical	Interactions with MurNac, phosphate cage and isoprenyl units	13
	BAS0012758	Preclinical	Interactions with MurNac, phosphate cage and isoprenyl units	42
	6Jc48-1	Preclinical	Interactions with MurNac, phosphate cage and isoprenyl units	43

Note: Data from references.^13–15