The enzyme porphobilinogen deaminase (PBGD; hydroxymethylbilane synthase; EC 2.5.1.61) catalyses an early step of the tetrapyrrole-biosynthesis pathway in which four molecules of the monopyrrole porphobilinogen are condensed to form a linear tetrapyrrole. The enzyme possesses a dipyrromethane cofactor which is covalently linked by a thioether bridge to an invariant cysteine residue. Expression ...

Dihydroxymethyl and monohydroxymethyl methylenecyclopropane nucleosides are effective inhibitors of both variants of human herpesvirus 6 (HHV-6). We investigated involvement of HHV-6 U69 protein kinase in their mechanism of action. Phosphorylation of the dihydroxymethyl analogue cyclopropavir and monohydroxymethyl nucleosides with either a 6-ether moiety (MBX 2168) or a 6-thioether moiety (MBX ...

A resin-capture and release strategy for making combinatorial 2,6,9-trisubstituted purine libraries is demonstrated by capturing N9-derivatized purines at the C6 position with a thio-modified polymer. The C2 fluoro group is subsequently substituted with primary and secondary amines followed by thioether oxidation and release by C6 substitution with amines and anilines. This approach complements...

Sulfur atoms are present as thiol and thioether functional groups in amino acids, coenzymes, cofactors, and various products of secondary metabolic pathways. The biosynthetic pathways for several sulfur-containing biomolecules require the substitution of sulfur for hydrogen at unreactive aliphatic or electron-rich aromatic carbon atoms. Examples discussed in this review include biotin, lipoic a...

The capsule of Bacillus anthracis, composed of poly-D-glutamic acid ( DPGA), is an essential virulence factor of B. anthracis. The capsule inhibits innate host defense through its antiphagocytic action. DPGA is a poor immunogen, but when covalently bound to a carrier protein, it elicits serum antibodies. To identify the optimal construct for clinical use, synthetic DPGAs of different lengths we...

Plantaricin W (Plw) is a new two-peptide bacteriocin, from Lactobacillus plantarum, which inhibits a large number of Gram-positive bacteria. The two peptides, Plwalpha (comprising 29 residues) and Plwbeta (comprising 32 residues), were isolated from the culture supernatants and characterized. The individual peptides had low antimicrobial activity but acted synergistically, and synergism was see...

New cationic Ag(I) complexes were prepared by reaction of AgBF4 with two thioether-functionalized bis(diphenylphosphino)amine ligands, Ph2PN(p-ArSMe)PPh2 (L1) and Ph2PN(n-PrSMe)PPh2 (L2), and compared with those obtained from the unfunctionalized ligands Ph2PN(Ph)PPh2 (L3) and Ph2PN(n-Bu)PPh2 (L4), respectively. The complex [Ag3(μ3-Cl)2(μ2-L1-P,P)3](BF4) (1·BF4) contains a triangular array of A...