Chemical Biology

LEAPT: Lectin-directed enzyme-activated prodrug therapy

Robinson et al. describe a glycosylation-based system for cell-specific activation of a prodrug compound. A nonmammalian enzyme, α-rhamnosidase, is artificially tagged with a carbohydrate that enables targeting to and internalization by cells of interest; following introduction of a similarly glycosylated, rhamnoside-capped prodrug, strong, tissue-specific enzymatic drug activation is observed.

Robinson, M.A. et al. Proc. Natl. Acad. Sci. USA 101, 14527–14532 (2004).

Bioinformatics

Textpresso: an ontology-based information retrieval and extraction system for biological literature

Müller et al. have devised a system for the analysis of text from the abstracts, titles and body of published articles, after which the data is organized ontologically according to established categories. This system, which the authors term Textpresso, makes it possible to conduct more productive and efficient literature searches.

Müller, H.-M. et al. PLoS Biol., published online 21 September 2004.

Gene Transfer

Self-inactivating retroviral vectors with improved RNA processing

Self-inactivating (SIN) vectors offer a safer alternative to conventional retroviruses for gene delivery, but typically suffer from reduced titer and inefficiency of RNA processing. Kraunus et al. have developed a modified SIN vector incorporating a favorable intron that considerably improves transgene expression from the construct, and a viral regulatory element that strongly elevates the titer.

Kraunus, J., et al. Gene Therapy, published online 16 September 2004.

Protein Biochemistry

The site-specific incorporation of p-iodo-L-phenylalanine into proteins for structure determination

Using a directed-evolution strategy, Xie et al. generated an orthogonal, variant tyrosyl-tRNA synthetase capable of specifically directing the incorporation of the unnatural amino acid p-iodo-L-phenylalanine at the amber stop codon in Escherichia coli. Introduction of this residue into proteins is shown to improve the quality of structure determination via single wavelength anomalous dispersion (SAD) phasing.

Xie, J. et al. Nat. Biotechnol., 22, 1297–1301 (2004).

Bioinformatics

Comparative homology agreement search: an effective combination of homology-search methods

Alam et al. introduce a tool called comparative homology agreement search (CHASE), which integrates five different sequence homology search methods to obtain a combined 'E value' confidence estimate for homology that surpasses the analytical performance of any of the individual algorythms.

Alam, I. et al. Proc. Natl. Acad. Sci. USA 101, 13814–13819 (2004).