Benzyl Side Chain Research Articles

Penicillin derivatives as monovalent elicitors of anaphylaxis: The importance of the thiazolidine moiety

Monohaptenic DNCP-hexamethylenediamine derivatives carrying benzoyl or phenylacetyl groups as auxiliary structures elicit cutaneous anaphylactoid reactions in guinea pigs passively sensitized with anti-DNCP antiserum. An analogous compound with benzylpenicilloyl as auxiliary group is a markedly better elicitor and evokes apparently standard PCA. This implies that the thiazolidine moiety of benzylpenicilloyl is a better auxiliary structure than the benzyl side-chain and may endow penicillin derivatives with the capacity to act as monovalent elicitors of anaphylaxis. This was confirmed by the finding that the ε-aminocaproate of N 6-DNP-aminopenicillanic acid is an elicitor of anaphylactoid reactions in guinea pigs passively sensitized against DNP.

Structure of 6-(2-phenethyl)purine, a synthetic cytokinin

C13H12N4, M r = 224, monoclinic, P21/c, a= 17.903 (2), b = 5.038 (4), c = 13.193 (3) A, fl= 93.89 (2) ° , D m = 1.25, D e = 1.255 Mg m -3, Z = 4, R = 0.088 on 1079 intensities. The molecule is extended with a trans conformation around the central C-C bond linking the purine and phenyl residues. The aromatic-ring planes are twisted roughly 90 ° with respect to the linking C-C bonds and the rings are twisted 14 ° to each other. Introduction. Cytokinin activity is exhibited by a large variety of N6-substituted adenine derivatives, natural and synthetic (Leonard, 1974). It has been demon- strated that compounds with the linking NH at C(6) replaced by CH 2, S, or O between the purine ring and, for example, the isopentenyl or benzyl side chain also possess cytokinin activity (Henderson, Frihart, Leon- ard, Schmitz & Skoog, 1975). The methylene analog of N6-(2-isopentenyl)adenine is about 20% as active as the natural cytokinin in the tobacco bio-assay, while N6-benzyladenine and 6-(2-phenethyl)purine (I) have nearly equal activity. Thus, an intact purine with an appropriate substituent at the 6 position is necessary and sufficient for cytokinin activity. It was of interest to compare the conformation of the phenethyl side chain directly attached to C(6) of the purine ring in (I) with the conformations that have been determined for the isopentenylamino C(6) substituent in the natural

An unusual cleavage of a side chain during catalytic hydrogenation of some octalones

Novel hydrogenolysis of a CC bond linking a benzyl side chain in some octalones is described.

Peptidic cyclols. Synthesis, and crystal and molecular structure of a tricyclic thia-cyclol

By following a three-step procedure, the linear peptide [(RS)-2-tritylthiopropionyl]-L-phenylalanyl-L-proline (6) has been converted into the cyclic derivative (9). On the basis of spectroscopic data and X-ray crystallographic analysis, compound (9) is shown to be a this-cyclol whose tricyclic system is related to the peptidic portion of the ergot alkaloids. Properties of the new compound are compared to those of previously studied peptidic aza- and oxa-cyclols. The thiazolidinono ring of (9) adopts in the crystal an approximate envelope conformation, whereas the pyrrolidine ring assumes a half-chair conformation. The benzylic side chain of the phenylalanine residue adopts in the crystal a folded conformation which seems to be preferred even in chloroform solution.

Inhibition of peptidoglycan transpeptidase by beta-lactam antibiotics: Structure-activity relationships.

The inhibitory activities of representative beta-lactam compounds, such as penicillins G and N, cephalosporins C and G, clavulanic acid, nocardicin A and thienamycin against Escherichia coli KN-126 and Bacillus megaterium KM peptidoglycan transpeptidases were studied. Their modes of action against E. coli are discussed on the basis of the results and the published binding data for penicillin binding proteins. The effects of modifications at position 3 and 7 of the cephalosporin and those at alpha-carbon of the benzyl side-chain of cephalosporin G and penicillin G were studied. The introduction of an amino group at this position in cephalosporin G together with the removal of an acetoxy group from the acetoxymethyl group at position 3 reduced the inhibitory activity against E. coli transpeptidase considerably. The activity was restored by the replacement of the methyl group at position 3 of cephalexin with chlorine. The restoration was accompanied by about 15-fold increase in the lytic activity of cephachlor against E. coli.

Structural studies of azacyclols derived from linear tripeptides

N-Benzyloxycarbonyl-L-alanyl-L-phenylalanyl-L-proline p-nitrophenyl ester (4) and its N-p-bromobenzyloxycarbonyl analogue (2) each cyclize in alkaline aqueous medium to give a tricyclic system containing a free hydroxy-group derived from intramolecular addition of NH to amide carbonyl. Both the five-membered rings of the tricyclic system assume an envelope conformation. In the six-membered ring only the carbon atom bearing the cyclolic hydroxy-group is out of the plane of the other ring atoms. The benzylic side-chain of the phenylalanine residue adopts an extended conformation in both azacyclols. The crystal and molecular structures and spectral data for the tricyclic compounds (3) and (5) are reported.

Design of potent and specific inhibitors of carboxypeptidases A and B

The combination in one molecule of functional groups that can interact specifically with different substrate binding areas at the active site of carboxypeptidases A and B has led to the development of potent and specific inhibitors of these enzymes. 2-Benzyl-3-mercaptopropanoic acid (SQ 14,603) has a Ki of 1.1 x 10(-8) M vs. carboxypeptidase A and a Ki of 1.6 x 10(-4) M vs. the B enzyme. 2-Mercaptomethyl-5-guanidinopentanoic acid (SQ 24,798) has a Ki of 4 x 10(-10) M vs. carboxypeptidase B and a Ki of 1.2 x 10(-5) M vs. carboxypeptidase A. It is proposed that the sulfhydryl groups of these inhibitors bind to the catalytically important zinc ions of these enzymes, and that, in conjunction with the benzyl and guanidinopropyl side chains, they are responsible for their specificity.

Heats of dissociation of mixture of poly(gamma-benzyl L- and D-glutamate).

The heats of dissociation of stacked side-chain benzyl groups in mixtures of various proportions of poly(gamma-benzyl L- and D-glutamate) have been measured by a differential scanning calorimeter. In order to obtain further information about the dissociation, the heats of solution of poly(gamma-benzyl L- and D-glutamate) were also measured by a twin micro calorimeter at 303 K. The agreement between the heat of dissociation obtained by DSC and that determined by the heat of dissolution is good. The average value of the heat of dissociation of stacking estimated by both methods is about 5 kJ/(mol of pairs of residue.

Self-association of benzylpenicillin in aqueous solution: 1H nuclear magnetic resonance study

Concentration dependence of 1H n.m.r. spectra suggests that benzylpenicillin ions aggregate in aqueous solution primarily through hydrophobic interactions of the benzyl side chains.

On the size of the active site in proteases II. Carboxypeptidase-A

The size of the active site of carboxypeptidase-A was investigated by studying the kinetics of hydrolysis of peptides of L-alanine, D-alanine and L-phenylalanine, as well as of a number of their N-benzyloxycarbonyl, N-acetyl, N-phenylproprionyl and N-methyloxycarbonyl derivatives. From a comparison of the various kinetic parameters ( K m, k cat) it was concluded that the active site of this enzyme extends over about 18 Å. The binding area can be divided into 5 “subsites”, each accommodating one amino acid residue (or blocking group) of the substrate. By comparing K m values of pairs of substrates containing either a methyl or a benzyl side-chain in equivalent positions, it was shown that the binding area as a whole has a larger affinity towards the aromatic residues. Substitution of a D-residue for an L-residue reduced k cat values rather than K m. In addition a remarkable affinity for the urethane-grouping located specifically at subsite S 3 was found. A methyloxycarbonyl or benzyloxy — carbonyl group occupying this subsite caused a 5-fold increase in K m as compared with an acetyl or phenylproprionyl group, respectively. Methyloxycarbonyl or benzyloxycarbonyl groups in subsites S 2 or S 4 showed no such effect.

Polypeptides. XIV. The synthesis of some oligopeptides containing lysine and glutamic acid residues.

Several oligopeptides of the general formula A-Ly[graphic omitted].(or [graphic omitted]lu).Glyn.[graphic omitted]lu.(or [graphic omitted]ys).Glyn.OB have been synthesised; their projected use for polymerisation experiments and for “doubling” imposes limitations on the protecting groups which can be used, since these must be selectively removable. In two cases, it was not found possible to remove an N-formyl group without breaking peptide linkages, while in these and a further case, selective removal of other protecting groups was prevented by the great lability of side-chain benzyl ester groups towards alkali. Finally, four protected oligopeptides of the required type were synthesised, using benzyloxycarbonyl for α-N-protection, t-butyl ester for ω-C-protection, and trifluoroacetyl and methyl ester for the protection of lysine and glutamic acid side-chains, respectively. Three of these were converted into side-chain protected peptides suitable for polymerisation and into the free peptides, and two of them, by a “doubling” procedure into the octa- and dodeca-peptides.