The formylglycine generating-enzyme (FGE) recognizes and acts specifically on a pentapeptide (CXPXR), oxidizing the cysteine to an unusual aldehyde bearing formylglycine residue (fGly). This conversion to fGly is possible when the sequence is inserted into recombinant proteins. The small FGE target sequence, termed the 'aldehyde tag', anchors the Redwood Bioscience technology that can generate homogenous, enhanced biotherapeutics. This platform provides the site specificity and chemical flexibility needed to generate useful post translational modifications on virtually any protein. This ability o affix novel chemical functionalities to a biological entity of interest is an immensely powerful platform for the development and optimization of new therapeutics. As applications of this technology are explored it will be advantageous to have flexibility in the consensus sequence recognized by FGE, so as to permit the modification of as many protein targets as possible, ideally on sites that exist already in their endogenous sequences. A panel of FGE enzyme/tag pairs would be an incredibly powerful platform and generate valuable intellectual property. The new tag sequences will be designed to minimize perturbation of the protein sequence and maximize FGE specific activity, thereby enabling optimized conjugation. This new tag technology will generate bioconjugates with minimal antigenicity and enhanced pharmacokinetics. Towards this end, Redwood Bioscience will embark on a research program using a directed evolution approach with yeast cell surface protein display to generate FGE variants that recognize unique and novel substrates.
Thesaurus Terms: Adhesions;Adverse Effects;Aerobic;Agglutinins;Aldehydes;Amino Acid Sequence;Base;Biological;Biological Assay;Biological Response Modifier Therapy;Businesses;Catalysis;Cell Surface;Cell Surface Proteins;Cells;Chemicals;Commercial Application;Complex;Consensus Sequence;Cysteine;Design;Development;Directed Evolution;Drug Kinetics;Engineering;Enzyme Activity;Enzyme Substrate;Enzymes;Expression Vector;Flexibility;Flow Cytometry;Fluorescence-Activated Cell Sorting;Fluorescent Dyes;Formylglycine;Generations;Hand;Human;Immune Response;Immunofluorescence Immunologic;In Vitro;In Vivo;Intellectual Property;Interest;Label;Lead;Libraries;Methods;Modification;Monitor;Mutant;Novel;Novel Therapeutics;Overexpression;Peptide Sequence Determination;Peptides;Phase;Plasmids;Positioning Attribute;Post-Translational Protein Processing;Pressure;Process;Programs;Proteins;Public Health Relevance;Recombinant Proteins;Recombinants;Redwood;Research;Saccharomyces Cerevisiae;Serum Albumin;Site;Specificity;Surface;Synthetic Peptide;System;Technology;Testing;Therapeutic;Therapeutic Protein;Treatment Efficacy;Variant;Yeasts;
