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Abstract

The insulin-like growth factor-I (IGF-I) is a key regulator of skeletal muscle growth in vertebrates, promoting mitogenic and anabolic effects through the activation of the MAPK/ERK and the PI3K/Akt signaling pathways. Also, these results show that there is a time-dependent regulation of IGF-I plasma levels and its signaling pathways in muscle. The insulin-like growth factor-I (IGF-I) is a key regulatory hormone that controls growth in vertebrates. Particularly, skeletal muscle growth is strongly stimulated by this hormone. IGFI stimulates both proliferation and differentiation of myoblasts, as well as promoting myotube hypertrophy in vitro and in vivo. The mitogenic and anabolic effects of IGF-I on muscle cells are mediated through specific binding with the IGF-I receptor (IGF-IR). This ligand-receptor interaction promotes the activation of two major intracellular signaling pathways, the mitogen-activated protein kinases (MAPKs), specifically the extracellular signal-regulated kinase (ERK), and the phosphatidylinositol 3 kinase (PI3K)/Akt. The MAPK (RAF/MEK/ERK) is a key signaling pathway in skeletal muscle, where its activation is absolutely indispensable for muscle cell proliferation. Biologically active polypeptides derived from the E domain that forms the C-terminus of the insulin-like growth factor I (IGF-I) splice variant known as mechano growth factor which have been demonstrated neuroprotective and cardioprotective properties, as well as the ability to increase the strength of normal and dystrophic skeletal muscle. Ligands selected from phage-displayed random peptide libraries tend to be directed to biologically relevant sites on the surface of the target protein. Protein-peptide interactions form the basis of many cellular processes. Consequently, peptides derived from library screenings often modulate the target protein’s activity in vitro and in vivo and can be used as lead compounds in drug design and as alternatives to antibodies for target validation in both genomics and drug discovery. In this research and science project we for the first time a predicted chemo-polypharmacophoric agent comprising (Propeptide-Fc)/MGF peptide mimicking properties for the possible increasement of the Muscle Mass Fiber Size towards Wnt7a/Fzd7 Signalling to the Akt/mTOR Anabolic Growth IGF-I/PI3K/Akt -I/MAPK/ERK pathways utilising (Propeptide-Fc)/MGF phage-displayed random peptide libraries through a KNIME-RDkit-CDK clustering pipeline.

Article Type

Research Article – Abstract

Publication history

Received: Sep 20, 2017
Accepted: Sep 25, 2017
Published: Oct 01, 2017

Citation

Grigoriadis Ioannis, Grigoriadis George, Grigoriadis Nikolaos, George Galazios (2017) A predicted chemo-polypharmacophoric agent comprising (Propeptide-Fc)/MGF peptide mimicking interactive of high free binding energy properties towards Wnt7a/Fzd7 signalling Akt/mTOR anabolic growth IGF-I/PI3K/Akt -I/MAPK/ERK pathways.

Authors Info

Grigoriadis Nikolaos
Department of IT Computer Aided Personalized Myoncotherapy, Cartigenea-Cardiogenea, Neurogenea-Cellgenea, Cordigenea-HyperoligandorolTM,
Biogenea Pharmaceuticals Ltd,
Thessaloniki, Greece;

Grigoriadis Ioannis
Department of Computer Drug Discovery Science, BiogenetoligandorolTM,
Biogenea Pharmaceuticals Ltd,
Thessaloniki, Greece;

Grigoriadis George
Department of Stem Cell Bank and ViroGeneaTM,
Biogenea Pharmaceuticals Ltd,
Thessaloniki, Greece;

George Galazios
Professor of Obstetrics and Gynecology,
Democritus University of Thrace,
Komotini, Greece;

E-mail: biogeneadrug@gmail.com

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