This review covers the structure and function of heparin and heparan sulfate glycosaminoglycans. Their chemical structures are discussed, including recently developed methods for sequencing picomole to nanomole quantities of heparin- and heparan sulfate-derived oligosaccharides. The biosynthesis of heparin and heparan sulfate is reviewed as it relates to their diverse and varied structures, and their biological activities and functions are discussed. The literature up to August 2001 is reviewed, and 208 references are cited.

We explore strategies to enhance conformational ordering of N-substituted glycine peptoid oligomers. Peptoids bearing bulky N-alkyl side chains have previously been studied as important examples of biomimetic "foldamer" compounds, as they exhibit a capacity to populate helical structures featuring repeating cis-amide bonds. Substantial cis/trans amide bond isomerization, however, gives rise to conformational heterogeneity. Here, we report the use of N-aryl side chains as a tool to enforce the presence of trans-amide bonds, thereby engendering structural stability. Aniline derivatives and bromoacetic acid are used in the facile solid-phase synthesis of a diverse family of sequence-specific N-aryl glycine oligomers. Quantum mechanics calculations yield a detailed energy profile of the folding landscape and substantiate the hypothesis that the presence of anilide groups establishes a strong energetic preference for trans-amide bonds. X-ray crystallographic analysis and solution NMR studies verify this preference. Molecular modeling indicates that the linear oligomers can adopt helical structures resembling a polyproline type II helix. High resolution structures of macrocyclic oligomers incorporating both N-alkyl and N-aryl glycine units confirm the ability to direct the presence of trans-amide bonds specifically at N-aryl positions. These results are an important step in developing strategies for the rational de novo design of new structural motifs in biomimetic oligopeptoid systems.

The binding of cadmium, zinc, lead, and mercury ions by the tripeptide glutathione has been investigated by carbon-13 magnetic resonance spectroscopy. Binding to the potential coordination sites was monitored as a function of solution conditions by observing the chemical shifts of the carbon atoms of glutathione. The results indicate that each of these metal ions binds to the potential coordination sites of glutathione with a high degree of specificity, with the actual sites involved in metal binding being dependent on the metal ion and the solution pD, with the exception of mercury which binds only to the sulfhydryl group at a mercury to glutathione ratio up to 0.5. At a metal to glutathione ratio of 0.5, Cd2+ and Zn2+ bind to both the sulfhydryl group and the amino group, the extent of binding to the two different sites being a function of pD, while Pb2+ binds only to the sulfhydryl group. Some binding of the glutamyl and glycyl carboxylic acid groups to cadmium, zinc, and lead was detected in certain pH regions. The chemical shift data for the carbonyl carbons of the two peptide linkages suggest zinc-promoted ionization of the peptide protons with subsequent binding of zinc to the ionized peptide nitrogen at pD greater than 10.5, while no evidence for this metal-promoted reaction was observed in the cadmium, lead, and mercury complexes. The results are discussed in terms of the possible structures of the complexes.

No abstract

The biological activities of N-substituted glycine oligomers (peptoids) have been the subject of extensive research. As compared to peptides, both the cis and trans conformations of the backbone amide bonds of peptoids can be significantly populated. Thus, peptoids are mixtures of configurational isomers, with the number of isomers increasing by a factor of 2 with each additional monomer residue. Here we report the results of a study of the kinetics and equilibria of cis/trans isomerization of the amide bonds of N-acetylated peptoid monomers, dipeptoids, and tripeptoids by NMR spectroscopy. Resonance intensities indicate the cis conformation of the backbone amide bonds of the peptoids studied is more populated than is generally the case for the analogous secondary amide bond to proline residues in acyclic peptides. Rate constants were measured by inversion-magnetization transfer techniques over a range of temperatures, and activation parameters were derived from the temperature dependence of the rate constants. The rate of cis/trans isomerization by rotation around the amide bonds in the peptoids studied is generally slower than that around amide bonds to proline residues and takes place on the NMR inversion-magnetization transfer time scale only by rotation around the amide bond to the C-terminal peptoid residue.