Plant cystine‐knot peptides: pharmacological perspectives

Cystine‐knot miniproteins are a class of 30–50 amino acid long peptides widespread in eukaryotic organisms. Due to their very peculiar three‐dimensional structure, they exhibit high resistance to heat and peptidase attack. The cystine‐knot peptides are well represented in several plant species including medicinal herbs and crops. The pharmacological interest in plant cystine‐knot peptides derives from their broad biological activities, mainly cytotoxic, antimicrobial and peptidase inhibitory and in the possibility to engineer them to incorporate pharmacophoric information for oral delivery or disease biomonitoring. The mechanisms of action of plant cystine‐knot peptides are still largely unknown, although the capacity to interfere with plasma membranes seems a feature common to several cystine‐knot peptides. In some cases, such as potato carboxypetidase inhibitor (PCI) and tomato cystine‐knot miniproteins (TCMPs), the cystine‐knot peptides target human growth factor receptors either by acting as growth factor antagonist or by altering their signal transduction pathway. The possibility to identify specific molecular targets of plant cystine‐knot peptides in human cells opens novel possibilities for the pharmacological use of these peptides besides their use as scaffold to develop stable disease molecular markers and therapeutic agents.