No abstract

{2‐[(4‐Methoxyphenyl)telluro]ethyl}amine and bis(2‐aminoethyl) telluride on treatment with o‐hydroxyacetophenone gave the Schiff bases 4‐MeOC6H4TeCH2CH2N=C(CH3)C6H4‐2‐OH (L1) and 2‐HOC6H4(CH3)C=NCH2CH2TeCH2CH2N=C(CH3)C6H4‐2‐OH (L3), respectively. The reduction of L1 and L3 with NaBH4 resulted in 4‐MeOC6H4TeCH2CH2NHCH(CH3)C6H4‐2‐OH (L2) and 2‐HOC6H4(CH3)CHNHCH2CH2TeCH2CH2NHCH(CH3)C6H4‐2‐OH (L4), respectively, which have 1 or 2 chiral centers. The 1H and 13C NMR spectra of L1 to L4 were found to be characteristic. Treatment of L1 with [Ru(p‐cymene)Cl2]2 resulted in [Ru(p‐cymene)(4‐MeOC6H4TeCH2CH2NH2)Cl]Cl·H2O (1) whereas in the reaction of L2 with [Ru(p‐cymene)Cl2]2, the p‐cymene ligand is lost resulting in [RuCl(L2‐H)] (4). The reactions of L1, L3 and L4 with HgBr2 resulted in complexes of the type [HgBr2·(L)2] while Na2PdCl4 reacted with L1 to give [PdCl(L1‐H)]. The solid‐state structures of L1, L3, 1 and 4 were determined by single‐crystal X‐ray diffraction studies. The very swift formation of the tellurated amine from a tellurated Schiff base (L1) by hydrolysis has been observed for the first time and has resulted in 1. The Ru−N and Ru−Te bond lengths in 1 are 2.142(3) and 2.6371 (4) Å, respectively. The replacement of the p‐cymene ligand with a hybrid organotellurium ligand (L2‐H), resulting in 4, is also a first example of its kind. The Ru center in 4 has a square‐planar geometry, with the Ru−N, Ru−Te, Ru−O and Ru−Cl bond lengths being 2.041(6), 2.4983(8), 2.058(5) and 2.308(2) Å, respectively. In the crystals of 4 there are secondary intermolecular Te···Cl interactions and intermolecular N−H···O hydrogen bonds. This is the first example in which coordinated Te in a complex is engaged in two intermolecular secondary interactions. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

No abstract

The transcription terminator Rho regulates many physiological processes in bacteria, such as antibiotic sensitivity, DNA repair, RNA remodeling, and so forth, and hence, is a potential antimicrobial target, which is unexplored. The bacteriophage P4 capsid protein, Psu, moonlights as a natural Rho antagonist. Here, we report the design of novel peptides based on the C-terminal region of Psu using phenotypic screening methods. The resultant 38-mer peptides, in addition to containing mutagenized Psu sequences, also contained plasmid sequences, fused to their C termini. Expression of these peptides inhibited the growth of Escherichia coli and specifically inhibited Rhodependent termination in vivo. Peptides 16 and 33 exhibited the best Rho-inhibitory properties in vivo. Direct high-affinity binding of these two peptides to Rho also inhibited the latter's RNA-dependent ATPase and transcription termination functions in vitro. These two peptides remained functional even if eight to ten amino acids were deleted from their C termini. In silico modeling and genetic and biochemical evidence revealed that these two peptides bind to the primary RNA-binding site of the Rho hexamer near its subunit interfaces. In addition, the gene expression profiles of these peptides and Psu overlapped significantly. These peptides also inhibited the growth of Mycobacteria and inhibited the activities of Rho proteins from Mycobacterium tuberculosis, Xanthomonas, Vibrio cholerae, and Salmonella enterica. Our results showed that these novel anti-Rho peptides mimic the Rho-inhibition function of the 42-kDa dimeric bacteriophage P4 capsid protein, Psu. We conclude that these peptides and their C-terminal deletion derivatives could provide a basis on which to design novel antimicrobial peptides.