Platelet-derived growth factor (PDGF) was discovered in 1974 as a peptide regulator that stimulates the growth of tissue cells such as connective tissue. It is named because it is derived from platelets. It exists in the alpha granules of platelets under normal physiological conditions. When blood coagulates Released from disintegrating platelets and activated, it has the biological activity of stimulating the chemotaxis of specific cells and promoting the growth of specific cells. In addition, macrophages, vascular smooth muscle cells, fibroblasts, endothelial cells, embryonic stem cells, etc. can also synthesize and release PDGF when tissues are damaged. When the liver is damaged, macrophages, platelets, infiltrating inflammatory cells, damaged endothelial cells and activated hepatic stellate cells can secrete PDGF. The common platelet-derived factor PDGF is a homo- or hetero-dimer formed by two polypeptide chains connected by disulfide bonds, which makes PDGF have various forms of dimer structures, namely PDGF-AA, PDGF-BB, PDGF -AB, PDGF-CC and PDGF-DD. The molecular weight of PDGF-A chain is 16KD, and the PDGF-B chain is 14KD. The A and B chain genes are located on chromosomes 7 and 22, respectively.

Figure 1. PDGF binding and signaling pathways. ( Evrova O, et al.; 2017)

PDGF include four members, PDGF-A, PDGF-B, PDGF-C and PDGF-D. They act as potent mitogens in a variety of mesenchymal cells (e.g., fibroblasts, vascular smooth muscle cells) and play important roles in the regulation of embryonic development, cell proliferation, migration, survival, and chemotaxis, and are associated with A variety of diseases are closely related. At present, researchers have detected highly expressed or mutated PDGFR receptors and highly expressed PDGFs in a variety of tumors, fibrosis, and cardiovascular diseases.  Therefore, it is more appropriate to select PDGF as a drug target to treat tumors in tumor therapy. CD ComputaBio provides PDGF targeting services to customers to accelerate their research progress.

Our Services

• Targeted Protein Structural Analysis

Using X-ray single crystal diffraction technology and the 3D structure of the known homologous molecule to simulate the structure of the PDGF molecule, and then infer its binding site;  

• Analysis of Target Protein Properties

Our experienced professional researchers use state-of-the-art molecular simulation software to analyze the structural properties of the PDGF binding site, such as electrostatic field, hydrophobic field, hydrogen bonding site distribution, etc.;

• Lead Candidate Search

Use database search software or new drug molecular design technology to screen lead compounds whose molecular morphology and physicochemical properties match the action site of PDGF;  

• Candidate Compound Validation

These molecules are synthesized and tested for biological activity, and after several screening cycles, suitable lead compounds can be found.

Our Advantage

• We can help you accelerate and enable hit identification, hit rates, optimize ADME and toxicology profiles, and predict any safety issues.
• Work with CD ComputaBio's Computer-Aided Drug Design (CADD) team to put leading informatics, virtual screening and molecular modeling expertise at your fingertips.
• Our experienced team works closely with our colleagues in medicinal chemistry, screening and structural biology to support projects and play a leading role in the design of our fragment and compound libraries.
• Parts or individual services of our CADD functional services are offered as stand-alone products.

Our Capabilities

In each therapeutic area, CD ComputaBio has accumulated deep expertise in discovery informatics, computational chemistry/molecular modeling, medicinal chemistry, structural biology, in vivo andin vitro pharmacology, and translational science. During the drug discovery process, our team focuses on early lead compounds in different target classes and uses a wide range of techniques, including molecular screening, molecular modeling, medicinal chemistry, structural biology, bioinformatics and computational chemistry, to identify new target the direction of drug development, and then select suitable drug candidates through low-cost, high-efficiency computer simulations to ensure high efficiency and low risk in the later drug development process. Our computational biology team has extensive experience in the research of PDGF targets. Please consult our professional team for details.

References

1. Andrae J, et al.; Role of platelet-derived growth factors in physiology and medicine. Genes Dev. 2008, 22: 1276–1312
2. Junkunlo K, et al.; PDGF/VEGF-related receptor affects transglutaminase activity to control cell migration during Crustacean hematopoiesis. Stem Cells Dev. 2017, 26: 1449–1459.
3. Hannink M, et al.; Structure and function of platelet-derived growth factor (PDGF) and related proteins. Biochim. Biophys. Acta. 1989, 989 (1): 1–10.
4. Heldin CH. Structural and functional studies on platelet-derived growth factor. EMBO J. 1992, 11 (12): 4251–4259.
5. Evrova O, et al.; In vitro and in vivo effects of PDGF-BB delivery strategies on tendon healing: a review. Eur Cell Mater. 2017, 34:15-39.