Boutique chemical manufacturing of homogeneous glycopeptides.
Chemitope Glycopeptide, LLC, or Chemitope, is a boutique biotech company that aims to produce a new generation of preventative vaccines. Chemitope was founded by Dr. Baptiste Aussedat and Dr. William Walkowicz, two PhD scientists at Memorial Sloan Kettering Cancer Center in New York City, to meet the current and future demand for homogeneous glycopeptides in the ongoing effort to develop an HIV vaccine.
For decades, the dense layer of carbohydrates present on viral glycoproteins, known as the 'glycan shield', was viewed by the scientific community as an elaborate protection mechanism to evade the immune system. However, reverse vaccinology, which is emerging as the new paradigm in challenging vaccine development, has made that 'shield' one of its primary targets. We believe that chemically defined homogeneous glycopeptides are essential for the induction of a broadly neutralizing antibody response against insidious viruses like HIV, Hepatitis C, and Influenza.
We specialize in the design and synthesis of complex homogeneous glycopeptides, which can accurately mimic a domain or a motif of a viral glycoprotein. Our highly efficient chemical synthesis process allows for atomic-level control of the targeted glycopeptidic construct, and the incorporation of various post-translational modifications and unnatural amino acids.
Experts in Glycopeptide Engineering
The team at Chemitope Glycopeptide has extensive experience in the chemical synthesis of challenging glycopeptides and full-length glycoproteins. Our flexible methods allow for the incorporation of homogeneous natural and unnatural N- and O-glycosylation motifs along with unnatural amino acids and post-translational modifications, including, sulfation, phosphorylation, and methylation.
Our technology to produce synthetic glycopeptides relies on the paradigm of convergent N-linked glycopeptide assembly depicted in the figure below and exemplified by the chemical synthesis of the HIV broadly neutralizing V3 epitope mimic. This technology offers us the possibility to access glycopeptidic structure regardless of the glycosylation sites' relative position in the sequence, the nature of the glycan of interest (complex-type or high-mannose) and the nature of the appended entities (adjuvants, T-helper peptide, functional handle) required for the full potentiation of these immunogens.
In the case of the HIV, shown below, a single glycoprotein, Env, coats the entire surface of the virion. Over the last decade, several sites of vulnerability have been identified at the surface of Env, opening the path towards a prophylactic HIV vaccine. Among the sites known to induce a broadly neutralizing antibody (bnAb) response, the most promising are glycopeptidic epitopes (V1V2 region, V3 loop) comprising both peptide and glycan moieties. To build an effective immune response against these key epitopes, immunization should be carried out with glycopeptides that share these characteristic features. Thus, generation of an accurate glycopeptide epitope mimic involves the conceptual excision of the motif of interest from the native glycoprotein, with the aid of structural data from X-ray, cryo-electron microscopy, or nuclear magnetic resonance spectroscopy. From there, the Chemitope team designs and synthesizes a conformationally stable glycopeptide, which is subsequently probed for antigenicity and iteratively improved by substituting sub-optimal residues and modulating the nature of the glycosylation motifs.
Once the targeted sequence is synthesized and successfully validated through antigenicity studies, the epitope mimic can be:
Selectively functionalized to improve immunogenicity (adjuvants, T-helper epitope, multimerization) and formulated for immunization
Used for structural studies with X-ray crystallography, cryo-EM, or NMR spectroscopy
Used for isolation of unknown bnAbs from infected patient sera, as shown in Science Translational Medicine.
Recent publications from the Chemitope Team
Our specialty is the synthesis of challenging glycopeptides. We can produce micrograms to hundreds of milligrams of homogeneous glycopeptide, which can be functionalized in almost limitless ways. For examples, see our publications in the Journal of the American Chemical Society and Science Translational Medicine (shown at right). We will work with your team to design candidate constructs to suit your needs. Contact us for a quote.
Our library of synthetic and semisynthetic glycans can be purchased for use in your custom application.
Customized linker (PEGx, succinate, etc)
Functional handle (azide, alkyne, thiol, amine, etc)
Tag (FITC, cascade blue, etc)