Sulfur-containing Side Chains Research Articles

ChemInform Abstract: Reaction Mechanisms in the Radiolysis of Peptides, Polypeptides, and Proteins

The purpose of this review is to bring together and to correlate the wide variety of experimental studies that provide information on the reaction products and reaction mechanisms involved in the radiolysis of peptides, polypeptides and proteins (including chromosomal proteins) in both aqueous and solid-state systems. The comparative radiation chemistry of these systems is developed in terms of specific reactions of the peptide main-chain and the aliphatic, aromatic-unsaturated and sulfur-containing side-chains. Information obtained with the various experimental techniques of product analysis, competition kinetics, spin-trapping, pulse radiolysis and ESR spectroscopy is included. 147 refs.

Structure-activity relationships of sparsomycin: modification at the hydroxyl group

Ten analogues of the antibiotic sparsomycin were prepared and evaluated in several in vitro tests. Nine of them carry a modification at the hydroxymethylene group of the molecules, two have a disulfide bond instead of the S(O)-CH 2-S moiety at the sulfur-containing side chain of the molecules. While the presence of the S-S group decreases the activity of the analogues in all the tests performed, the modification at the OH group has no deleterious effects on the activity when a polyphenylalanine synthesis assay is used in an Escherichia coli extract. The same modifications, however, diminish drastically the activity of the analogues when tested in a similar Saccharomyces cerevisiae extract. A polymerization system in the archaebacterium Halobacterium halobium extract behaves like the eukaryotic preparations. A discrepancy is also found between the results of the polymerization tests and those of the ‘puromycin reaction’ which is also less sensitive to the modified sparsomycin analogues. The results of cell growth inhibition tests in bacteria as well as in eukaryotic organisms agree only partially with the in vitro data.

Studies on the structural requirenents for synthetic formyl peptide chenoattractants

Seven small molecular weight new peptides related to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (CHO-Met-Leu-PheOH) have been prepared by classical peptide synthesis. Compounds were prepared by classical peptide synthesis. Compounds were prepared to evaluate the requirements at the C-terminal Phe group. Each analogue tested for its ability to induce lysosomal enzyme release from human neutrophils. The following new derivative of CHO-Met-Leu-Phe-R were prepared, where R is ▪ Chemotactic peptides have generated considerable interest in recent years. These peptides are of particular importance because they represent a mean of studying cellular immune responses using a defined pure material in contrast to ill-defined chemotactic factors of unknown composition (Wilkinson .1974) . Since Showell et al. (1976) have shown that N -formyl tripeptides are chemotactic towards rabbit peritoneal polymorphonuclear leucocytes, numerous structure-activity studies have been undertaken, in order to investigate the structural requirements for maximum pharmalogical activity of chemotactic peptides related to the standard chemotactic peptide N-formyl-methionyl-phenylalanine (FMLP). From these studies, five structural requirements for optimal activity of chemotactic peptides have been delineated. The N -formyl group is essential for good activity (Freer . 1980), the sulfur-containing side chain of position 1 methionine produces optimum activity of the tripeptide (Freer. 1980), the leucine side chain appears to be less restricted than for the methionine side chain however the branching at the carbon may be of importance (Freer . 1982), the phenylalanine side chain resides in an hydrophobic pocket of limited depth since para-substitutions on the phenylalanine ring markedly reduce biological activity (Wilkinson. 1974) (Day . 1977), the carbonyl function of the Phe residue seems to be required for good biological activity. Freer et al. (1982) proposed a critical interaction of the Phe C=0 with the receptor, possibly via hydrogen bonding. This final point appears to be less clear that the understanding of other structural requirements. Indeed, in 1978, Ho et al. reported that the methyl ester of CHO-Met-Leu-Phe-OH is more active in stimulating macrophage chemotaxis than the parent carboxylic compound, although it is less active against neutrophils. Morever addition of a lysine residue (i.e. CHO-Met-leu-Phe-Lys-OH) has relatively little effect on the biological activity against rabbit neutrophils (Freer . 1980). More recently, Freer et al. (1982) showed that the analogue in which the carboxyl group of the Phe residue was eliminated was only slightly active whereas the benzylamide and benzyl ester of CHO-Met-Leu-Phe-OH are even more potent than the parent compound. In order to provide new informations about the role of the phenylalanine carbonyl residue, we have undertaken a classical synthesis of new peptides, and the purpose of this comunication is to describe our results on the potency of these new peptides on the induction of lysosomal enzyme release from human leucocytes.

Enthalpies of ligand binding to bovine neurophysins.

Flow microcalorimetry and batch microcalorimetry have been used to survey the energetics of ligand binding by bovine neurophysins I and II. Calorimetry studies were supplemented by van't Hoff analyses of binding constants determined by circular dichroism. Free energies of binding of a series of di- and tripeptides that bind to the strong hormone binding site of neurophysin were partitioned into their enthalpic and entropic components. The results indicate that, at 25 degrees C, the binding of most peptides is an enthalpy-driven reaction associated with negative entropy and heat capacity changes. Studies elsewhere, supported by evidence here, indicate that the principal component of the negative enthalpy change does not arise from the increase in neurophysin dimerization associated with peptide binding. Accordingly, the negative enthalpy change is attributed to direct bonding interactions with peptide and possibly also to peptide-induced changes in tertiary or quaternary organization. Comparison of the binding enthalpies of different peptides indicated two types of bonding interactions that contribute to the negative enthalpy change of peptide ligation. Substitution of an aromatic- or sulfur-containing side chain for an aliphatic side chain in position 1 of bound peptides led to increases in negative enthalpy of from 1 to 6 kcal/mol, demonstrating that interactions typically classified as hydrophobic can have a significant exothermic component at 25 degrees C. Similarly, loss of hydrogen bonding potential in the peptide decreased the enthalpy change upon binding, in keeping with the expected enthalpic contribution of hydrogen bonds. In particular, the data suggested that the peptide backbone between residues 2 and 3 and the phenolic hydroxyl group in position 2 participate in hydrogen bonding.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of sparsomycin analogs on the puromycin-peptidyl transferase reaction on ribosomes

Sparsomycin analogues in which the unique -S(O)CH2SCH3 moiety was replaced by a variety of more easily accessible side chains were evaluated as inhibitors of the peptidyl transferase reaction with bacterial ribosomes. Competitive inhibition of acetyl[14C]phenylalanylpuromycin formation revealed that the sulfur-containing side chain of sparsomycin could be replaced with hydrophobic moieties, whereas complete removal of the -S(O)CH2SCH3 side chain eliminated the ribosomal binding affinity of sparsomycin. The specificity for the D isomer of S-deoxo-S-propylsparsomycin has established that the chiral carbon of sparsomycin analogues must be identical with the chirality of D-cysteinol for ribosomal binding.

Purification and comparative mechanistic studies of an endogenous inhibitor of maize RNA polymerase

1. A low molecular weight inhibitor of maize DNA-dependent RNA polymerase (nucleoside triphosphate: RNA nucleotidyltransferase, EC 2.7.7.6) has been purified to chromatographic homogeneity from a high-speed supernatant fraction which also contains the soluble enzyme. 2. Chemical characterization of the inhibitor has revealed the presence of an aromatic nucleus which apparently contains an attached —COOH group and one or more sulfur-containing side chains. 3. Studies using known inhibitors of RNA polymerase for comparative purposes demonstrated that the maize inhibitor acts much the same as α-amanitin in its ability to interrupt polymerization. Initiation by maize RNA polymerase was greatly enhanced in the presence of the maize inhibitor. 4. On the basis of resistance to rifamycins and inhibition by α-aminitin, the soluble maize RNA polymerase was shown to be equivalent to the nucleoplasmic RNA polymerase II of animals.

Compounds with Some Sulfur-containing Side-chains

Compounds with Some Sulfur-containing Side-chains