Kisspeptins and their synthetic analogues: structure, mechanism of action and prospects for clinical use
PATHOPHYSIOLOGY — MEDICINE
Abstract
The literature review compares native kisspeptin (KP) and its synthetic analogues, including modifications that improve its stability in the human body, and characterizes the possibility of their therapeutic use in the correction of reproductive disorders. KP is a key neuropeptide that regulates reproductive function through activation of the KISS1R receptor and stimulation of gonadotropin-releasing hormone (Gn RH) secretion. It was found that kisspeptin-10 and kisspeptin-54 have different pharmacokinetics, but KP-10 activates the KISS1R receptor no less effectively. The mechanism of action of CP is associated with the activation of the Gq/11 protein cascade, leading to an increase in intracellular calcium and activation of phospholipase C. Modifications of kisspeptins that improve their stability are described, including the replacement of amino acids, the addition of protective groups that slow down degradation and can significantly increase the half-life of the peptide in the blood. The main areas of application of kisspeptins in clinical practice, including in the treatment of reproductive disorders and oncology, are considered. Synthetic analogues of kisspeptin, especially those modified to improve stability, are of significant interest for the development of new therapeutic strategies in the field of reproductive medicine. Synthetic analogs of KP that are resistant to degradation by matrix metalloproteinases (MMP-2/9) are being developed. Phosphine analogs that inhibit MMP and prolong the half-life are promising.
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