Quantum Chemical and Molecular Mechanics Studies on the Binding of Stereoisomers of the Oligopeptide Antibiotics Amidinomycin and Noformycin to the Minor Groove of B-DNA
Abstract:Ab initio calculations (Hartree-Fock) using the 6-31G basis set have been performed on two chiral oligopeptide antitumor antibiotics amidinomycin 5 and noformycin 6. The latter are DNA minor groove binding agents related to the A.T recognizing netropsin 4 and distamycin 3 but, unlike the latter, bear stereocenters (two for 5 and one for 6) that may be expected to affect binding to the B-DNA receptor. Geometry optimized conformations, energies and distribution of electrostatic charges within the molecules were … Show more
“…The antibiotics termed kikumycins A ( 5 ) and B ( 6 ) − (from Streptomyces phaeochromogenes) , noformicin ( 7 ) (from Nocardia formica ), and anthelvencin A ( 8 ) , (from Streptomyces venezuelae ) have also been represented as having structures with the tautomeric 5-iminoprolyl moiety. These compounds have antimicrobial, and also antiviral activity, especially noformicin. , Their biological activity is exerted through binding to the minor groove of DNA. , …”
Section: Dehydroprolinesmentioning
confidence: 99%
“…82 The lincomycins have been reviewed. 83 (22) of unreported streochemistry is a component of the peptide lactone antibiotic hormaomycin (from Streptomyces griseoflavus), which is active against some Grampositive bacteria, especially Arthrobacter species. 84,85 It has potent aerial mycelium-inducing activity.…”
Section: B 4-substituted Prolines 4-methylproline Cis-mentioning
“…The antibiotics termed kikumycins A ( 5 ) and B ( 6 ) − (from Streptomyces phaeochromogenes) , noformicin ( 7 ) (from Nocardia formica ), and anthelvencin A ( 8 ) , (from Streptomyces venezuelae ) have also been represented as having structures with the tautomeric 5-iminoprolyl moiety. These compounds have antimicrobial, and also antiviral activity, especially noformicin. , Their biological activity is exerted through binding to the minor groove of DNA. , …”
Section: Dehydroprolinesmentioning
confidence: 99%
“…82 The lincomycins have been reviewed. 83 (22) of unreported streochemistry is a component of the peptide lactone antibiotic hormaomycin (from Streptomyces griseoflavus), which is active against some Grampositive bacteria, especially Arthrobacter species. 84,85 It has potent aerial mycelium-inducing activity.…”
Section: B 4-substituted Prolines 4-methylproline Cis-mentioning
“…We reported the application and utility of this approach to prototype lexitropsins (21). Certain chiral oligopeptide antibiotics, due to their smaller size were subjected to the complete optimization of the entire molecule (22). The present study concerns the application of this method to Hoechst 33258, the prototype benzimidazole 1.…”
Ab initio calculations (Hartree-Fock) using the 3-21G and the STO-3G Gaussian basis sets were performed on the sequence selective minor groove binding bis-benzimidazole Hoechst 33258. Geometry optimized conformations, energies and distribution of electrostatic charges within the molecule were derived. The binding of the optimized conformations of the drug to both alternating and non-alternating (AT)n sequences was studied.
SummaryThe natural amidinomycin ((W, 35)-14) and its three stereoisomers are synthesized from homochual3-oxocyclopentanecarboxytic acids (la) by asymmetric methods, which are based on an asymmetric reductive amination to produce methyl cis-N-( 1 -phenylethyl)-3-aminocyclopentanecarboxylates (3b) via optically active me thy1 N-( l-phenylethyl)-3-iminocyclopmtane-carboxylates (2b) for the cis-isomers of 14. Optically pure trum-3-aminocyclopentane-carboxylic acids (4a) are obtained from the homochiral keto acids la via asymmetric reductive amination of 3-hydroxyiminocyclopentanecarboxytic acids (Sa) and lead to the tmns-isomers of 14.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.