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In clinical culture media inoculated with patient samples, selective inhibition of commensal bacteria is essential for accurate diagnosis and effective treatment, as they can mask the presence of pathogenic bacteria. The alanine analogue, 1-aminoethyltetrazole was investigated as a potential alanine racemase inhibitor. For effective uptake and enhanced and selective antibacterial activity, a library of C-terminal 1-aminoethyltetrazole containing di- and oligopeptides were synthesized by solid phase peptide coupling techniques. The investigation of the antimicrobial activity of the synthesised compounds identified several clinically applicable selective inhibitors. These enabled differentiation between the closely related bacteria, Salmonella and Escherichia coli, which can be difficult to discriminate between in a clinical setting. In addition, differentiation between enterococci and other Gram-positive cocci was also seen.

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For the first time a number of terminally protected model peptides (to the pentamer level) of the sterically demanding alpha-amino acid Calpha-methyl, Calpha-diphenylmethylglycine, (alphaMe)Dip, in combination with either Ala or Gly residues, have been synthesized (by solution methods) and fully characterized. In a parallel synthesis the corresponding peptides based on the related alpha-amino acid Calpha-methyl, Calpha-isopropylglycine, (alphaMe)Val, have also been prepared. The results of a comparative conformational analysis, performed by using FTIR absorption, 1H NMR, and X-ray diffraction techniques, favour the conclusion that, in contrast to the potent beta-turn and 310-helix promoter (alphaMe)Val, (alphaMe)Dip may induce either a folded or a fully extended conformation. These findings indicate that, despite the common Calpha-methylated and Cbeta-branched features, (alphaMe)Dip and (alphaMe)Val are characterized by partially divergent conformational bias.

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A benzyloxycarbonyl protected glycine equivalent 2 has been prepared in enantiopure form and has been used in the synthesis of both alpha-substituted amino acids and alpha,alpha-disubstituted amino acids. The process involved deprotonation to form the corresponding enolates which underwent stereoselective alkylation with various electrophiles and upon hydrolysis gave the corresponding amino acid derivatives as enantiomerically pure products.

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Enantiomerically pure 4-substituted 2-aralkyl-2,4-dihydro-1H-pyrazino[2,1-b]quinazoline-3,6-diones (1b-m) in which the alkyl chain is (CH2)n, n = 1-3, behave as glycine templates giving by treatment with [hydroxy(tosyloxy)iodo]benzene in ethyl acetate cis-1-tosyloxy derivatives. When these compounds contain electron-rich aryl substituents with n = 2, they spontaneously cyclize through intramolecular Friedel-Crafts-type diastereoselective reactions to give penta- or hexacyclic compounds. Otherwise, they give by solvolysis cis-1-alkoxy derivatives, which in a second step, may be cyclized in acid if n = 2, 3. All these reactions must occur through N-acyliminium species in SN1-like mechanisms. 1-Alkoxy-2-arylmethyl derivatives are reluctant to cyclize, giving trans-1-hydroxy compounds as the only isolated reaction products.

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A novel macrobicycle featuring an amidopyridine unit as a carboxylic acid binding site, and amide functionality to provide further hydrogen bonding interactions with suitable guests has been prepared. The ability of this novel macrobicycle to bind peptide derivatives has been investigated.

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Methods for preparation of p-amidinophenyl esters from amino acid derivatives are described.Blocking of the amidino function with the benzyloxycarbonyl group and its deblocking by catalytic hydrogenation after coupling were satisfactory. p-Amidino-phenyl esters are of special interest because of their susceptibility to the hydrolytic enzyme, trypsin, and some parameters of the hydrolysis of these compounds by tripsin are presented.Keywords – p-amidinophenyl ester; synthetic substrates; ester formation; trypsin; enzyme kinetics; deacylation rate constant

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With respect to the hydrolysis (deacylation) of Z-D(L)-amino acid esters (N-(benzyloxycarbonyl)-D(L)-amino acid p-nitrophenyl esters) mediated by alpha-, beta- and gamma-cyclodextrins (CyDs), a remarkably high enantioselectivity (L/D=9.0) was observed for the deacylation of Ala substrate with gamma-CyD. The kinetic results on the basis of the Michaelis-Menten principle indicate that the enantioselectivity should be mainly originated in the deacylation process of substrates following the formation of gamma-CyD-substrate (1 : 1) complexes. The computer modeling (molecular mechanics) studies on the inclusion complexes are also described.

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A large rate enhancement and a stereoselective preference are exhibited in the hydrolysis catalysed by N-decanoyl-L-histidine (2a) and a dipeptide containing L-histidyl residue (2b) in the domain of linear poly(ethylimine) derivatives.

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Disclosed are compounds of the general formula: wherein R1 is amino, an acylated amino or a protected amino group, X is hydrogen or methoxy, and R is hydrogen, R or R4 where R is an organic residue attached to the azetidine ring through a carbon atom therein and R4 is azido, a halogen, an amino group which may optionally be acylated or a group of the formula wherein R5 is an organic residue and n is 0, 1 or 2, and pharmaceutically acceptable salts and esters thereof. The compounds have antimicrobial and/or beta-lactamase-inhibitory activity and are of value as drugs for human beings and domesticated animals

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N,N’-Diacyldiaza-18-crown-6 ethers were obtained by the acylation of diaza-18-crown-6 with amino acids.The enantioselectivity coefficients were determined for the chiral compound in relation to the L and D isomers of valine.The obtained compounds represent a promising class of enantioselective complexones.

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