Combinatorial chemistry with a newly‐developed screening procedure using complementary fluorescein‐ and rhodamine‐labelled oligonucleotides (below) has been used to select peptide dsDNA binding ligands. A high structure–affinity relationship of the dsDNA‐binding unnatural peptide was observed.

Sprays with high density of unsolvated biomolecule ions that are produced within an electrospray ionization (ESI) plume under ambient conditions are discussed by R. Zenobi and co‐workers in their Communication on The method substantially enhances the experimental arsenal for probing the intrinsic properties biomolecules.

(1 3.11.96) 2'-Deoxy-5-(isothiazol-5-yl)uridine (12) was synthesized starting from 2'-deoxy-5-iodouridine using a Pdcatalysed cross-coupling reaction with propiolaldehyde diethyl acetal followed by deprotection and ring closure using thiosulfate. 2'-Deoxyuridine 12 has a particular place among the 5-heteroaryl-substituted 2'-deoxyuridines in that it has a high affinity for herpes simplex virus type 1(HSV-1)-encoded thymidine kinase (TK) without antiviral activity. Biochemical studies revealed that 12 is a substrate for viral TK. We further investigated the interaction of 12 with the HSV-1 thymidine kinase. The conformation of 12 in solution was established by NMR spectroscopy. The most stable conformer 12A has the S-atom of the isothiazole ring placed in the neighbourhood of the C(4)=0 group of the pyrimidine moiety. The compound was docked in its most stable conformation in the active site of HSV-1 TK and subjected to energy minimization. This demonstrated that the isothiazole moiety binds in a cavity lined by the side chains ofTyr-132, Arg-163, Ala-167, and Ala-168 and that the C(3) atom of the isothiazole moiety is located in close proximity of the phenolic 0-atom of Tyr-132 and the aliphatic part of the Arg-163 side chain.Introduction. -The structure-activity-relationship study of 5-substituted 2'-deoxyuridines started with the historical discovery of 2'-deoxy-5-iodouridine as an anti-herpes agent [l]. The mode of action of 5-substituted 2'-deoxyuridines has since long been studied, and it is well documented that these compounds have to be phosphorylated to their mono-, di-, and triphosphate and that these metabolites are responsible for the biological activity. In their monophosphate form, some 5-substituted 2'-deoxyuridines are efficient inhibitors of thymidylate synthase [2]. In their triphosphate form, these nucleosides interfere with DNA synthesis by inhibiting DNA polymerases and/or by functioning as alternative substrates thus being incorporated into DNA. Whatever the mechanism, the first step in the anabolism to the active metabolite is the phosphorylation by nucleoside kinases. With respect to the 5-substituted 2'-deoxyuridines that are active against HSV-1, this phosphorylation is carried out by the viral thymidine kinase. The thymidine kinase (TK) encoded by herpes simplex virus type 1 (HSV-1) has a broader substrate specificity than the human enzymes so that modified nucleosides can be selectively activated in the HSV-1-infected cells.Recently, a study was undertaken to analyse the affinity of several 5-substituted 2'-deoxyuridines for the HSV-1-encoded TK and to relate this affinity with structural data [3-81. In Table I , an overview is given of the compounds synthesized (see Scheme for general Formula), together with their TK affinity. Compounds with a low affinity for the