The Development of Novel Antibiotics Using ... - Jacobs University

Computational studies
In order to further understand the nature of the host/guest interactions, we performed molecular
modeling simulation for host/guest complex 42 at the Austin Model 1 (AM1 level) using Hyper-
Chem software (Release 8.0) (Fig. 9). [29,30] It can be inferred from the minimised energy
structure that the carbonyl group of the carbamate moiety (NCOOC 2 H 5 ) in macrocycle 32 binds
the hydroxyl group (COOH) of the COOH terminal Glycine in oligopeptide 39 via hydrogen
bonding. Also, the amidic proton (NHCO) in macrocycle 32 binds the amidic carbonyl (NHCO)
of D-Alanine in peptide 39 through hydrogen bonding. Furthermore, the side chain of L-lysine is
embedded within the cavity of the macrocycle. This forms a stable host/guest complex and
suggests that macrocycle 32 can show promising antibacterial activity.
Figure 9. Computed structure for host/guest complex 42 at the AM1 level using a Polak-Ribiere conjugate gradient
with rms < 0.01 kcal.mol –1 .
CONCLUSIONS
ESI-TOF MS is an enormously versatile technique for studying non-covalent interactions and
providing vital information about the reactive reaction intermediates, which cannot be obtained
from other analytical instruments. Tetra-carbohydrazide cyclophane 32 forms a stable host/guest
complex with oligopeptide 39.
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