Suzanne Walker

Remarkable Structural Similarities between Diverse Glycosyltransferases

From a functional standpoint, glycosyltransferases (GTases) comprise one the most diverse group of enzymes in existence. Every category of biopolymer (oligosaccharides, proteins, nucleic acids, and lipids) plus numerous natural products are modified by GTases, with remarkably varied effects. Given the structural and functional diversity of the products of glycosyl transfer combined with the often distant evolutionary relationships between glycosyltransferases, it is not surprising that sequence homologies between glycosyltransferases are low. What is surprising is that the majority of glycosyltransferases belong to only two structural superfamilies, implying that nature has come up with only a few solutions to the ubiquitous problem of how to catalyze glycosyl transfer. The conservation of GTase structure suggests that it will be simpler to manipulate glycosyltransferases for various applications than previously envisioned. A new age in glycoconjugate chemistry is beginning.

Substrate analogues to study cell-wall biosynthesis and its inhibition.

It has been known for more than 30 years that Lipid II is an intermediate in peptidoglycan synthesis. Recently, it has become apparent that it is also an important target of numerous antibiotics, including the glycopeptides, the lantibiotics and ramoplanin. It is also utilized by sortases in the construction of Gram-positive cell walls. Recent progress has been made in the synthesis of peptidoglycan intermediates that can be used to study enzymes which make peptidoglycan. These intermediates also enable studies to probe the mechanism of action of a variety of substrate-binding antibiotics.

NMR characterization of calicheamicin γ1I bound to DNA

Abstract Calicheamicin γ1I is a diyne-ene antitumor antibiotic that binds preferentially to pyrimidine-rich sequences of DNA such as TCCT, ACCT, TCTC,

Chemistry and cellular aspects of cationic facial amphiphiles

A series of compounds containing a bile acid core and a polyamine side chain have been synthesized to evaluate their ability to promote the uptake of DNA into cells. These compounds differ from conventional cationic lipids because they contain a positively charged chain attached to a facial amphiphile rather than to a hydrophobic moiety. Formulations of several of the designed compounds were found to dramatically increase the cellular uptake of both plasmid and oligonucleotide DNA. Moreover, initial experiments have shown that some of the compounds promote plasmid gene expression in various tissues after introduction into animals. These results have provided interesting information about structure-activity relationships as well as clues to the mechanism of action that may lead to further improvements in the design.

Conjugates of Glycosylated Steroids and Polyamines as Novel Nonviral Gene Delivery Systems

We have designed novel glycosteroid-polyamines for transmembrane DNA delivery based on amphiphilic drug transport agents. These glycosteroid-based agents show promise as viable DNA delivery technology for gene therapy.