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In Vitro Imaging and Quantification of the Drug Targeting Efficiency of Fluorescently Labeled GnRH Analogues
Published on: March 21, 2017
Human chorionic gonadotropin: a model molecule for oligopeptide-based drug discovery
Nisar Ahmed Khan1, Robbert Benner
1Department of Immunology, Erasmus MC University Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands. n.khan@erasmusmc.nl
Endocrine, Metabolic & Immune Disorders Drug Targets
|March 1, 2011
Summary
Small protein fragments, called oligopeptides, derived from human chorionic gonadotropin (hCG) show regulatory potential. These peptides can inhibit inflammation, diabetes, and cancer, with one accelerating recovery from radiation in mice.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Small protein fragments (oligopeptides) can possess regulatory functions in biological systems.
- The pregnancy hormone human chorionic gonadotropin (hCG) is a source of such regulatory oligopeptides.
- These oligopeptides are derived from specific sites within the β-hCG subunit.
Purpose of the Study:
- To investigate the role of selected oligopeptides derived from β-hCG in (patho)physiological systems.
- To design and test novel oligopeptides based on β-catenin and C-reactive protein (CRP) structures.
- To explore the potential of these 'peptide-i' molecules as therapeutic agents.
Main Methods:
- Design of oligopeptides (3-7 amino acids) based on β-hCG 'loop-2' nick sites.
- Testing the inhibitory effects of oligopeptides on inflammation, type I diabetes, renal failure, and tumorigenesis.
- Evaluating an oligopeptide (AQGV) for its efficacy in accelerating recovery from lethal radiation in mice.
- Employing a systems biology approach to design oligopeptides targeting cell division genes in a plant model.
Main Results:
- Oligopeptides derived from β-hCG demonstrated inhibitory effects on severe inflammation, type I diabetes, renal failure, and tumorigenesis.
- One specific oligopeptide (AQGV) significantly improved survival rates in mice exposed to lethal radiation.
- This AQGV oligopeptide has successfully completed human Phase I and IIa clinical trials.
- Designed oligopeptides based on β-catenin and CRP structures inhibited vital cell division genes in plants, suggesting a conserved regulatory role.
Conclusions:
- Regulatory oligopeptides derived from hCG and other proteins represent a novel class of therapeutic molecules.
- The identified 'peptide-i' peptides interfere with gene expression, offering a new mechanism for biological regulation.
- These findings suggest a conserved, evolutionarily ancient regulatory system involving oligopeptides.
- Oligopeptide-based pharmaceuticals hold significant promise for addressing unmet therapeutic challenges.
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