Peptide Natural Products and Therapeutics

We have been interested in synthesizing new and proprietary amatoxins (amanitin analogs) that can be used as targeted payloads. We have identified a number of new amatoxins, some of which are covered by patent filings while others have freedom to operate as they are not protected by IP held by competing pharmaceutical corporations e.g. Huadong Pharmaceutical Group and Heidelberg Pharma. Below are two of a growing number of toxins that we are experimenting with. The first amatoxin (1) has an novel sulfilimine for altered but near-native cytotoxicity and provides a new handle for bioconjugation. Toxin-1 is currently IP-protected but we may released this to the public to encourage the use of amanitin for targeted therapy. Our other amatoxins e.g. (2), which show undisclosed selectivity against certain cell lines, are protected by patent filings. In each case, we are pleased to offer collaborative services to potential industrial partners.

We are investigating their use in targeted therapeutics. For example in ADCs, the use of amanitin leads to an ATAC (amatoxin-tethered antibody conjugate) while with peptides, the conjugate is called a PAC (peptide-amatoxin conjugate) and with DNA aptamers are called AptACs (aptamer tethered amanitin conjugates). We are using these to generate the next generation of ATACs and PACs as well as AptACs.