Lead is a nonessential, toxic metal widely spread in the environment and affects vast populations worldwide. It is thus ranked in the top ten chemicals of primary public health concern, and no blood lead level (BLL) is deemed safe. Lead at even very low concentrations shows destructive effects on various body organs. Nevertheless, health authorities determine threshold values from which environmental and medicinal interventions should occur. Most countries adopt the WHO recommendation of 5 µg/dL as this value. In the USA, the CDC reduced this value to 3.5 µg/dL, recognizing again the devastating effects of lead at any level.
Based on these values, 16% of the US children, every third child globally, and every second adult in the USA are poisoned with lead. While at highly acute poisoning, lead kills (almost 1 million annually worldwide), lower poisoning levels cause various symptoms and diseases, mainly kidney impairment, anemia, high blood pressure, and other cardiovascular failures, fertility issues for both genders, and most critically, cognitive and neurological damages. The brain and the central nervous system are most susceptible to lead poisoning since lead ions resemble calcium ions, which are highly essential in these organs. As a result, lead, as a neurotoxicant, easily crosses the blood-brain barrier, resulting in amplified damage to the brain.

The available treatments for lead poisoning are strongly limited in their applicability and are inefficient in reaching sensible threshold values. Simply put, most diagnosed patients cannot be treated medically.

metaLead‘s novel short peptides are designed to prioritize and strongly bind lead while leaving essential and physiologically relevant metal ions such as calcium, copper, zinc, and iron intact. We succeeded in tailoring such unique peptides that selectively and tightly bind lead ions by addressing the differences between the targeted metal and the essential ones in terms of their physical and coordination properties, including ionic radii, preferred coordination numbers, preferred ligands, and binding geometries.
A family of over 50 candidates was developed to target toxic metal ions, where each of its members was screened for its capabilities to detoxify lead. Successful members were then thoroughly investigated for their lead affinity, metal selectivity, other chemical and physical properties, and at last, efficacy and safety in mice.