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Joseph M Langenhan

Publications and source records attributed to Joseph M Langenhan.

7 recordsLinked to original sources
PubMed2005

'Sweetening' natural products via glycorandomization.

In an effort to explore the contribution of the sugar constituents of pharmaceutically relevant glycosylated natural products, chemists have developed glycosylation methods for the generation of 'glycorandomized' libraries. Each member of these libraries is uniquely differentiated by an attached carbohydrate. Recently, two complementary glycorandomization strategies have emerged: chemoenzymatic glycorandomization, a biocatalytic approach dependent upon the substrate promiscuity of enzymes to activate and attach sugars to natural products, and neoglycorandomization, an efficient one-step chemical sugar ligation reaction that does not require prior sugar protection or activation. These strategies are likely to have a significant impact on fundamental glycoscience and drug discovery.

Carbohydrate Conformation↗
PubMed2005

Enhancing the anticancer properties of cardiac glycosides by neoglycorandomization.

Glycosylated natural products are reliable platforms for the development of many front-line drugs, yet our understanding of the relationship between attached sugars and biological activity is limited by the availability of convenient glycosylation methods. When a universal chemical glycosylation method that employs reducing sugars and requires no protection or activation is used, the glycorandomization of digitoxin leads to analogs that display significantly enhanced potency and tumor specificity and suggests a divergent mechanistic relationship between cardiac glycoside-induced cytotoxicity and Na+/K+-ATPase inhibition. This report highlights the remarkable advantages of glycorandomization as a powerful tool in glycobiology and drug discovery.

Animals↗
PubMed2005

Neoglycorandomization and chemoenzymatic glycorandomization: two complementary tools for natural product diversification.

In an effort to explore the contribution of the sugar constituents of pharmaceutically relevant glycosylated natural products, chemists have developed glycosylation methods that are amenable to the generation of libraries of analogues with a broad array of glycosidic attachments. Recently, two complementary glycorandomization strategies have been described, namely, neoglycorandomization, a chemical approach based on a one-step sugar ligation reaction that does not require any prior sugar protection or activation, and chemoenzymatic glycorandomization, a biocatalytic approach that relies on the substrate promiscuity of enzymes to activate and attach sugars to natural products. Since both methods require reducing sugars, this review first highlights recent advances in monosaccharide generation and then follows with an overview of recent progress in the development of neoglycorandomization and chemoenzymatic glycorandomization.

Aldehyde-Lyases↗
PubMed2004

Effects of alternative side chain pairings and reverse turn sequences on antiparallel sheet structure in beta-peptide hairpins.

[structure: see text] We describe a series of beta-peptide hexamers that allow us to explore relationships between sequence and hairpin folding. Different reverse turn segments are compared at the central two positions, and the outer residues allow a variety of interstrand side chain-side chain pairings. NMR analysis in methanol demonstrates that several reverse turn and side chain pairing arrangements are compatible with antiparallel beta-peptide sheet structure; however, none of the beta-peptides folds in water.

Magnetic Resonance Spectroscopy↗
PubMed2003

The correct space group of NaPF6 x H2O.

The structure of sodium hexafluorophosphate monohydrate, NaPF(6) x H(2)O, has been inadvertently redetermined, revealing that the previously reported space group, Imma, was assigned incorrectly, with the a and b axes interchanged. The correct space group is Pnna. The program PLATON [Spek (2003). J. Appl. Cryst. 36, 7-13] suggested both Imma and Pmma as possible space groups, but only Pnna is consistent with the systematic absences. The inter-ionic and hydrogen-bonding interactions in the lattice form a three-dimensional network.

Journal Article↗
PubMed2003

Preparation of protected syn-alpha,beta-dialkyl beta-amino acids that contain polar side chain functionality.

We report the synthesis of syn-alpha,beta-dialkyl beta-amino acid derivatives suitably protected for solid-phase synthesis that give rise to residues containing positively charged lysine-like side chains. These amino acids, as well as syn-alpha,beta-dialkyl beta-amino acids that contain diverse hydrophobic side chains, are prepared in good de and ee. The key step in this route involves Davies's protocol for the conjugate addition of a chiral lithium amide to alpha,beta-unsaturated tert-butyl esters (Davies, S. G.; Ichihara, O.; Walters, I. A. S. J. Chem. Soc., Perkin Trans. 1 1994, 9, 1141). syn-alpha,beta-Dialkyl beta-amino acids are interesting building blocks because of their sheet-forming propensity and because of their presence in bioactive compounds.

Amino Acids↗