Human Chorionic Gonadotropin: A Model Molecule For Oligopeptide-Based Drug Discovery
Abstract:Small degradation products of proteins can have regulatory powers in biological systems. We have studied the role of selected oligopeptides derived from the pregnancy hormone human chorionic gonadotropin (hCG) in several (patho)physiological systems. The employed oligopeptides (3 up to 7 amino acids) were designed according to the known nick sites in ‘loop-2’ of β-hCG. These oligopeptides can inhibit severe inflammation, the onset of type I diabetes, renal failure and tumorigenesis. One of the oligopeptides (AQGV) appeared capable of accelerating recuperation after lethal radiation of mice, thereby reducing the number of deaths among the irradiated mice. This particular oligopeptide has already been successfully tested in human Phase I and IIa studies.
Regulating oligopeptides are not only released as a specific subset by degradation of the pregnancy hormone hCG, but also during the degradation of other body proteins and possibly also by transcription of so-called ‘non-coding’ mRNA. Based on a system's biology approach we designed a series of oligopeptides with particular physico-chemical properties based on the primary structure of β-catenin and C-reactive protein (CRP). Several of the designed oligopeptides were able to inhibit vital genes involved in cell division in a plant model. We call such oligopeptides with regulating activity ‘peptide- i’ peptides, referring to their ability to interfere with the expression of particular genes, and thus with the expression of the related biological activities. The fact that the selected oligopeptides can inhibit the multiplication of plant cells suggests that these peptides, through evolution, are part of a hitherto unknown conserved regulatory system. Based on the data presented we foresee the development of many new regulatory oligopeptide-based pharmaceuticals, which could be a serious option for addressing new therapeutic challenges.
Keywords: Th2 phenomenon; drugs; hCG; heterodimeric hCG; human chorionic gonadotropin; immunoregulation; oligopeptides; peptide-i; pregnancy hormone; protein degradation; regulatory oligopeptide; trophoblastic tumor
Document Type: Research Article
Publication date: March 1, 2011
- This journal is devoted to timely reviews of experimental and clinical studies in the field of endocrine, metabolic, and immune disorders. Specific emphasis is placed on humoral and cellular targets for natural, synthetic, and genetically engineered drugs that enhance or impair endocrine, metabolic, and immune parameters and functions. Topics related to the neuroendocrine-immune axis are given special emphasis in view of the growing interest in stress-related, inflammatory, autoimmune, and degenerative disorders.