Home  About us  Contact
 

Guanidine Derivatives (guanidine + derivative)

Distribution by Scientific Domains
Chemistry100%

Selected Abstracts

ChemInform Abstract: Synthesis, Structure and Biological Activities of Some Novel N-(4,6-Disubstituted-pyrimidin-2-yl)-N,- (trifluoromethylphenyl)guanidine Derivatives.

CHEMINFORM, Issue 49 2008
Feng-Qi He
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source]

Basicity of Guanidines with Heteroalkyl Side Chains in Acetonitrile

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 30 2008
Mirjana Eckert-Maksi
Abstract The pKa values of seven novel guanidine derivatives, six of them possessing heteroalkyl substituents capable of forming intramolecular hydrogen bonds, were determined in acetonitrile (MeCN) by using the UV/Vis spectrophotometric titration method. The obtained pKa values range from 24.7 to 27.2. The most basic among the studied guanidines was found to be by ca. 4 pKa units more basic than thewell-known superbase N1,N1,N3,N3 -tetramethylguanidine (TMG). The trends in the changes in the measured pKa values were compared with the experimental (determined by the extended kinetic method) and theoretical [B3LYP/6-311+G(2df,p)//B3LYP/6-31G(d)] gas-phase proton affinities. It was shown that basicity ordering of the bases with dimethylaminopropyl substituents in acetonitrile follows the trend encountered in the gas phase. However, this is not the case for the methoxypropyl-substituted guanidines indicating that in these molecules formation of the intramolecular hydrogen bonds is to large extent hindered due to solvation by acetonitrile.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source]

The phosphate site of trehalose phosphorylase from Schizophyllum commune probed by site-directed mutagenesis and chemical rescue studies

FEBS JOURNAL, Issue 5 2008
Christiane Goedl
Schizophyllum commune,,,-trehalose phosphorylase utilizes a glycosyltransferase-like catalytic mechanism to convert its disaccharide substrate into ,- d -glucose 1-phosphate and ,- d -glucose. Recruitment of phosphate by the free enzyme induces ,,,-trehalose binding recognition and promotes the catalytic steps. Like the structurally related glycogen phosphorylase and other retaining glycosyltransferases of fold family GT-B, the trehalose phosphorylase contains an Arg507-XXXX-Lys512 consensus motif (where X is any amino acid) comprising key residues of its putative phosphate-binding sub-site. Loss of wild-type catalytic efficiency for reaction with phosphate (kcat/Km = 21 000 m,1·s,1) was dramatic (,107 -fold) in purified Arg507,Ala (R507A) and Lys512,Ala (K512A) enzymes, reflecting a corresponding change of comparable magnitude in kcat (Arg507) and Km (Lys512). External amine and guanidine derivatives selectively enhanced the activity of the K512A mutant and the R507A mutant respectively. Analysis of the pH dependence of chemical rescue of the K512A mutant by propargylamine suggested that unprotonated amine in combination with H2PO4,, the protonic form of phosphate presumably utilized in enzymatic catalysis, caused restoration of activity. Transition state-like inhibition of the wild-type enzyme A by vanadate in combination with ,,,-trehalose (Ki = 0.4 ,m) was completely disrupted in the R507A mutant but only weakened in the K512A mutant (Ki = 300 ,m). Phosphate (50 mm) enhanced the basal hydrolase activity of the K512A mutant toward ,,,-trehalose by 60% but caused its total suppression in wild-type and R507A enzymes. The results portray differential roles for the side chains of Lys512 and Arg507 in trehalose phosphorylase catalysis, reactant state binding of phosphate and selective stabilization of the transition state respectively. [source]

Arginine-based structures are specific inhibitors of cathepsin C

FEBS JOURNAL, Issue 11 2000
Application of peptide combinatorial libraries
Novel synthetic peptide inhibitors of lysosomal cysteine proteinase cathepsin C have been designed through the use of soluble peptide combinatorial libraries. The uncovered structural inhibitory module consists of the N-terminal cluster of l -arginine residues. Its modification with d -amino acids or arginine derivatives did not increase the inhibition strength. Inhibitory potency of oligoarginines improves with the elongation of peptide chain reaching a maximum for octa- l -arginine. The oligoarginines specifically interact with the cathepsin C active site as shown by competitive-type inhibition kinetics (Ki , 10,5 m) and intrinsic fluorescence measurements. The inhibitory interaction of oligoarginines is established through the specific spatial contact of a net of guanidino groups in the arginine side-chains, as indicated by comparison with inhibitory action of low molecular mass guanidine derivatives (Ki , 10,3 m). Nonarginine polyionic compounds cannot mimic the inhibitory effect of oligoarginines. The arginine-based peptide inhibitors were selective towards cathepsin C among other cysteine proteinases tested. [source]