Table 3 Structure activity relationships of carbon-linked vancapticins

	Structure				MIC (µg mL⁻¹)
Id	MIE	EEPS	Linker	MRSA^a	MSSA^b	+50% HS^c	VISA^d	VRSA^e	MDR SP^f	VRE^g
1		Vancomycin		1	1	1	4	>64	1	>64
2		Telavancin		0.06	nd	0.5	0.25	1	0.06	2
3		Dalbavancin		0.03	≤0.016	8	1	16	0.09	>8
4		Daptomycin		2	1	3	12	3	2	16
5		Oritavancin		0.06	≤0.016	0.5	1	0.125	0.06	0.125
Effect of chirality—EEPS and linker
24	POB2K^h	KK	K-NHMe	<0.003	≤0.016	0.06	0.125	0.08	<0.003	0.5
25	POB2K^h	kk	K-NHMe	0.0007	nd	0.5	0.125	nd	0.015	2
26	POB2K^h	kK	K-NHMe	<0.003	nd	0.25	0.19	nd	<0.003	1.5
27	POB2K^h	Kk	K-NHMe	0.03	nd	0.25	0.75	nd	0.04	10
28	POB2K^h	KK	k-NHMe	<0.003	nd	0.06	0.125	nd	0.015	0.75
Effect of side chain length—EEPS and linker
24	POB2K^h	KK	K-NHMe	<0.003	nd	0.06	0.125	0.08	<0.003	0.5
27	POB2K^h	K-Dap	K-NHMe	0.0045	nd	0.375	0.0925	nd	0.016	1.5
28	POB2K^h	Dap-K	K-NHMe	0.0045	nd	0.25	0.155	nd	0.011	0.75
29	POB2K^h	Dap-Dap	K-NHMe	0.0045	nd	0.5	0.0925	nd	0.0085	0.75
30	POB2K^h	K-Dab	K-NHMe	<0.003	nd	0.06	0.0925	nd	<0.003	0.75
31	POB2K^h	Dab-K	K-NHMe	<0.003	nd	0.045	0.0925	nd	<0.003	0.375
32	POB2K^h	K-Orn	K-NHMe	<0.003	nd	0.19	0.0375	nd	<0.003	1
33	POB2K^h	Orn-K	K-NHMe	<0.003	nd	0.125	0.125	nd	0.007	1.5
34	POB2K^h	Orn-Orn	K-NHMe	<0.003	nd	0.25	0.0185	nd	<0.003	0.5
35	POB2K^h	KK	Orn-NHMe	<0.003	nd	0.16	0.25	nd	0.005	1.25
Effect of MIE on activity
36	nC9CO-ⁱ	KKK	K-OH	0.06	nd	0.06	0.75	0.75	0.06	8
18	nC10CO-	KKK	K-OH	0.045	nd	0.093	0.5	0.5	0.06	1.03
37	nC11CO-	KKK	K-OH	0.005	nd	0.03	0.06	0.75	<0.003	0.5
38	nC12CO-	KKK	K-OH	<0.003	nd	0.045	0.03	nd	<0.003	0.1875
17	nC13CO-	KKK	K-OH	<0.003	≤0.016	0.06	0.03	0.045	<0.003	0.125

^aMethicillin-resistant S. aureus ATCC 43300
^bMethicillin-sensitive S. aureus ATCC 29213
^cHuman serum
^dVancomycin intermediate S. aureus NRS1
^eVancomycin-resistant S. aureus NARSA VRS4
^fMultidrug-resistant S. pneumoniae ATCC 700677
^gVancomycin-resistant (VanA) Enterococcus faecium ATCC 51559
^h POB2K N,N′-bis(4-phenoxybenzoyl)-Lys
ⁱ nCxCO n-alkanoyl, nd not determined. MIC measurements are the median of a minimum of two independent determinations in duplicate

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