AnchorChem LLC: Pioneering Solutions to Create a Stable Supply Chain of Cyanopeptides and Cyanotoxins to Address Global Health Threats

Anchorchem Llc, Grosse Pointe Park MI

Investigators

Abstract

Harmful Algal Blooms (HABs), exacerbated by agricultural runoff, present a global threat due to the production of toxic cyanopeptides by cyanobacteria. Many cyanopeptides present significant risks to human health from air, drinking water and environmental exposure. Negative health effects of cyanopeptides include carcinogenesis and adverse impacts on human neurological, hepatic, cardiac, and gastrointestinal systems. Conversely, some cyanopeptides show promising biological activity, serving as leads for the development of novel therapeutics. Research progress, particularly in identifying the prevalence of these compounds in the environment and their health impacts, is unfortunately impeded by the scarcity of pure cyanopeptides and their high cost. The STTR grant application aims to address a critical gap in the field for a group of cyanopeptides called anabaenopeptins (ABPs). ABPs are abundant in HABs. Over 150 ABPs have been identified from freshwater and brackish environments, and many of these compounds are potent inhibitors of key human enzymes. Furthermore, recent research confirms that ABPs harm nematodes that are valuable in vivo models for studying human aging and development, indicating significant risks exist. Unfortunately, the current supply chain of ABPs is limited to just two compounds (ABP A and B). Without accessible analytical standards, other ABP congeners will remain undetected which is an issue because ABPs beyond A and B exhibit strong enzyme inhibition. Thus, significant risks to human health exist, particularly through environmental exposure, such as contaminated drinking water. Additionally, the lack of affordable research-grade materials hampers the ability of researchers around the globe to conduct critical biological studies needed to assess the health risks of ABPs and understand their exposure pathways. This limited availability of ABPs is primarily due to the current reliance on natural product isolation rather than adopting a synthetic approach. AnchorChem, an environmental and green chemistry company, proposes to address this unmet need by creating a stable and affordable supply chain of cyanopeptides through chemical synthesis. As preliminary data, we developed an innovative de novo chemical synthesis route capable of producing ABP congeners at scale. Specific Aims for this Phase I STTR grant are to: Aim 1: Produce >100 mg quantities of ABPs A, B, F and Oscillamide Y from common pentacyclic cores. Aim 2: Develop analytical reference standards for ABPs A, B, F and Oscillamide Y. Aim 3: Characterize inhibitory properties of ABPs A, B, F and Oscillamide Y on carboxypeptidases A (CPA) and B (CPB) and protein phosphatases I and IIA (PPI and PPIIa) using synthetically derived standards. Phase II plans are to scale up production of research-grade materials and expand production to cover additional ABPs, including isotopically labeled derivatives desperately needed for environmental monitoring. AnchorChem’s longterm goal is to support the validated detection of cyanopeptides and advance human health research by providing a stable, affordable supply of these critical chemicals for basic research.