TRH analogues containing C-terminal tioamide group and norvaline ([Nva2, Prot3] TRH) or norleucine ([Nle2, Prot3] TRH) in position 2 were synthesized and tested for hormonal and central nervous system (CNS) activities. Receptor binding studies revealed that the analogues neither bind to pituitary nor to brain TRH receptors. Accordingly, no TSH releasing activity was recorded. However, both anal...

Conventional basal insulin preparations have to be resuspended prior to injection and have low therapeutic efficacy and drawbacks like nocturnal hypoglycaemia. There is evidence supporting improved pharmacokinetic and pharmacodynamic profiles of basal insulin analogues, glargine and detemir as compared with NPH. Initiation and titration of basal insulin analogues helps patients to improve compl...

Cobalamin (Cbl, vitamin B-12) has been extracted and isolated from a number of animal tissues by using (i) reverse-affinity chromatography on R protein-Sepharose followed by adsorption to and elution from charcoal-coated agarose and (ii) paper chromatography. Radioisotope dilution assays showed that only 75-97% of the Cbl chromatographed in the position of crystalline Cbl. The remaining 3-25% w...

Methyltransferases (MTases) form a large family of enzymes that methylate a diverse set of targets, ranging from the three major biopolymers to small molecules. Most of these MTases use the cofactor S-adenosyl-l-Methionine (AdoMet) as a methyl source. In recent years, there have been significant efforts toward the development of AdoMet analogues with the aim of transferring moieties other than ...

Adenosine and uridine analogues functionalized with alkenyl or fluoroalkenyl chain at C5' were prepared employing cross-metathesis, Negishi couplings, and Wittig reactions. Metathesis of the protected 5'-deoxy-5'-methyleneadenosine or uridine analogues with six-carbon amino acids (homoallylglycines) in the presence of Grubbs catalysts gave nucleoside analogues with the C5'-C6' double bond. Alte...

A number of nicotinamide adenine dinucleotide analogues have been prepared in which the purine, pyridine, and ribose moieties have been modified (2-12). These analogues have proven to be valuable in studies dealing with the site of binding of the pyridine coenzyme to dehydrogenases, in elucidating the mechanism of dehydrogenases and the configuration of the pyridme coenzymes, and as indicators ...

Metal-superoxo species are involved in a variety of enzymatic oxidation reactions, and multi-electron oxidation of substrates is frequently observed in those enzymatic reactions. A CrIII -superoxo complex, [CrIII (O2 )(TMC)(Cl)]+ (1; TMC=1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), is described that acts as a novel three-electron oxidant in the oxidation of dihydronicotinamide adeni...

Analogues of the mRNA 5'-cap are useful tools for studying mRNA translation and degradation, with emerging potential applications in novel therapeutic interventions including gene therapy. We report the synthesis of novel mono- and dinucleotide cap analogues containing dihalogenmethylenebisphosphonate moiety (i.e. one of the bridging O atom substituted with CCl2 or CF2) and their properties in ...

The aim of this work was to develop a reliable and efficient analytical method to characterise and differentiate saxitoxin analogues (STX), including sulphated (gonyautoxins, GTX) and non-sulphated analogues. For this purpose, hydrophilic interaction liquid chromatography (HILIC) was used to separate sulphated analogues. We also resorted to ion mobility spectrometry to differentiate the STX ana...

Dense granules of platelets contain a high content of diadenosine 5',5'''-P1,P4-tetraphosphate (Ap4A). We have previously demonstrated an antithrombotic effect of this compound in a live rabbit model. In the present study we find that certain synthetic Ap4A analogues are superior to Ap4A in inhibiting ADP-induced aggregation of human platelets. Analogues having a P--C--P bridge located in the P...