G-CSF receptor-binding cyclic peptides designed with artificial amino-acid linkers

Shibata, Kenji; Maruyama-Takahashi, Kumiko; Yamasaki, Motoo; Hirayama, Noriaki

doi:10.1016/j.bbrc.2005.12.204

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…It is recognized that fusion proteins have varied affinity and anti-tumor activity compared to the original molecules, due in large part to the structural alterations of the fusion proteins [4,28-31]. The inter-peptide linkers can be optimized with computer-aided design [32].…”

Section: Discussionmentioning

confidence: 99%

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma

Zhang

Liu

Shang

et al. 2012

Theor Biol Med Model

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We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G4S)n (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G4S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: rn=[]AB()n−boldABO2+[]CD()n−CDO2+[]BC()n−BCst2. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity.

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Section: Discussionmentioning

confidence: 99%

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma

Zhang

Liu

Shang

et al. 2012

Theor Biol Med Model

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show abstract

“…The intracellular region contains three distinct motifs called Box 1, Box 2, and Box 3 and four tyrosine residues (704, 729, 744, and 764) that are essential for mitogenic signal transduction. GCSF requires four highly conserved cysteine residues in the N-terminal half region and the WSXWS motif in the cytokine receptor-homologous (CRH) domain to bind GCSFR and initiate signal transduction ( 11 ). Additionally, these four cysteine residues in combination with an additional four cysteine residues at the N-terminal provide eight potential sites for N-linked glycosylation ( 12 ).…”

Section: Structurementioning

confidence: 99%

A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer

et al. 2022

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Granulocyte colony-stimulating factor receptor (GCSFR) is a critical regulator of granulopoiesis. Studies have shown significant upregulation of GCSFR in a variety of cancers and cell types and have recognized GCSFR as a cytokine receptor capable of influencing both myeloid and non-myeloid immune cells, supporting pro-tumoral actions. This systematic review aims to summarize the available literature examining the mechanisms that control GCSFR signaling, regulation, and surface expression with emphasis on how these mechanisms may be dysregulated in cancer. Experiments with different cancer cell lines from breast cancer, bladder cancer, glioma, and neuroblastoma are used to review the biological function and underlying mechanisms of increased GCSFR expression with emphasis on actions related to tumor proliferation, migration, and metastasis, primarily acting through the JAK/STAT pathway. Evidence is also presented that demonstrates a differential physiological response to aberrant GCSFR signal transduction in different organs. The lifecycle of the receptor is also reviewed to support future work defining how this signaling axis becomes dysregulated in malignancies.

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“…Like G-CSF, SB 247464 induced tyrosine phosphorylation of multiple signaling proteins and stimulated formation of granulocytic colonies and increased blood neutrophil counts in mice by dimerizing the external domains of the G-CSF receptor chains. 39,40 This concept continues to be explored 41 but has not been proven to be clinically applicable.…”

Section: Other Modificationsmentioning

confidence: 99%

Neutrophil Biology and the Next Generation of Myeloid Growth Factors

Dale¹

2009

J Natl Compr Canc Netw

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Neutrophils are the body's critical phagocytic cells for defense against bacterial and fungal infections. The bone marrow must produce approximately 10 × 109 neutrophils/kg/d to maintain normal blood neutrophil counts. Production of neutrophils depends on myeloid grow factors, particularly granulocyte colony-stimulating factor (G-CSF). After the original phase of development, researchers modified these growth factors to increase their size and delay their renal clearance, increase their biologic potency, and create unique molecules for business purposes. Pegylated G-CSF is a successful product of these efforts. Researchers have also tried to identify small molecules to serve as oral agents that mimic the parent molecules, but these programs have been less successful. In 2006, the European Medicines Agency established guidelines for the introduction of new biologic medicinal products claimed to be similar to reference products that had previously been granted marketing authorization in the European community. In Europe these products are called bio-similars. Throughout the world, new version and copied version of G-CSF and other myeloid growth factors are now appearing. Some properties of the myeloid growth factors are similar to other agents, offering opportunities for the development of alternative drugs and treatments. For example, recent research shows that hematopoietic progenitor cells can be mobilized with a chemokine receptor antagonist, chemotherapy, G-CSF, and granulocyte macrophage colony-stimulating factor. Advances in neutrophil biology coupled with better understanding and development of the myeloid growth factors offer great promise for improving the care of patients with cancer and many other disorders.

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G-CSF receptor-binding cyclic peptides designed with artificial amino-acid linkers

Cited by 7 publications

References 18 publications

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma

A review of granulocyte colony-stimulating factor receptor signaling and regulation with implications for cancer

Neutrophil Biology and the Next Generation of Myeloid Growth Factors

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