Rabuka D.,Redwood Bioscience Inc
Current Opinion in Chemical Biology
In the past decade, numerous chemical technologies have been developed to allow the site-specific post-translational modification of proteins. Traditionally covalent chemical protein modification has been accomplished by the attachment of synthetic groups to nucleophilic amino acids on protein surfaces. These chemistries, however, are rarely sufficiently selective to distinguish one residue within a literal sea of chemical functionality. One solution to this problem is to introduce a unique chemical handle into the target protein that is orthogonal to the remainder of the proteome. In practice, this handle can be a novel peptide sequence, which forms a 'tag' that is selectively and irreversibly modified by enzymes. Furthermore, if the enzymes can tolerate substrate analogs, it becomes possible to engineer chemically modified proteins in a site-specific fashion. This review details the significant progress in creating techniques for the chemoenzymatic generation of protein-small molecule constructs and provides examples of novel applications of these methodologies. © 2010 Elsevier Ltd. Source
Redwood Bioscience Inc | Date: 2014-11-26
The present disclosure provides conjugate structures and hydrazinyl-pyrrolo compound structures used to produce these conjugates. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 136.28K | Year: 2014
DESCRIPTION (provided by applicant): 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 developmentand 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, id
Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE II | Award Amount: 961.37K | Year: 2012
This Small Business Innovation Research (SBIR) II project outlines in vivo testing of semi-synthetic therapeutic protein conjugates. Low molecular weight peptide drugs have had limited therapeutic utility due to rapid clearance and, consequently must be injected very frequently. These drugs could be conjugated to a carrier protein. Attachment to large biomolecules, such as carrier proteins, improves the half-life profile of these peptides. Historically, many of these carrier proteins are recombinant genetic fusions with the peptide of interest. With fusion, the carrier?s attachment to the peptide is limited to one site, the end terminus, and that limited placement can impact drug function and thus potency. As an alternative, chemical modification to carrier proteins with small molecule drugs can also render the drug more potent and longer lasting. The scientists at Redwood Bioscience have developed a technology platform that can universally modify proteins in a controlled, site-specific manner. They have generated carrier protein scaffolds, modified recombinant Fc domains that are homogeneous and easy to chemically elaborate with therapeutic peptides. Furthermore, optimized peptide conjugation to the Fc proteins improves conjugate activity in vitro. This technology is to be further validated through an initial in vivo analysis.
The broader impacts of this research are the development of best in class therapeutics and the generation of a robust protein modification platform. This work will change the utility of protein therapeutics by enabling optimization of therapeutic peptides that otherwise would not be useful as treatment for disease.
Redwood Bioscience Inc | Date: 2013-03-11
The present disclosure provides conjugate structures (e.g., polypeptide conjugates) and hydrazinyl-indole compounds used to produce these conjugates. The disclosure also provides methods of production of such conjugates, as well as methods of using the same.