For Research Use Only. Not for Clinical Use.

Creative Biolabs is a leading service provider that focuses on half-life extension for drug development. Based on our advanced platforms and extensive experience, now we can provide CTP half-life extension services for our clients all over the world.

Introduction of Carboxyl-Terminal Peptide (CTP)

The previous studies showed that the half-life of human chorionic gonadotropin (hCG) is significantly longer than that of other heterodimeric glycohormones, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH). The major reason is the hCG β-subunit (HCG-β) contains a CTP with approximately 31 amino acid residues so that form four O-glycosylation sites terminating with a sialic acid residue. Sialic acids are negatively charged monosaccharides. Recombinant therapeutic peptides or proteins with negative surface charges will be repelled by the negatively charged polysaccharides on the glomerular filter membrane, resulting in slower renal clearance and a prolonged half-life.

Fig 1. Increasing the negative charge of therapeutic peptides and proteins by the introduction of glycosylation sites or fusion to CTP can also prolong half-life. (Tan, 2018)

Applications of Carboxyl-Terminal Peptide (CTP) in Half-Life Extension

In the past decades, CTP has been fused to a series of hormones, cytokines, and factors to elongate their half-lives. Compared with wild-type erythropoietin (EPO), the recombinant EPO-CTP produced by the fusion of CTP and the C-terminal gene of EPO showed significantly improved half-life and improved in vivo efficacy. FSH-CTP is the first CTP fusion protein to be included in clinical trials as a long-acting FSH to treat female infertility. Compared with wide-type FSH, its half-life is increased by two times, whether it is administered subcutaneously or intravenously. The hGH-CTP chimera formed by gene fusion of CTP and hGH has a 12-fold increase in the half-life in human serum.

In summary, CTP can be used as a module fused to the end of a peptide or protein to extend the half-life without affecting the receptor binding affinity or in vitro biological activity.

Advantages of CTP in Half-Life Extension

• Good applicability for multiple peptides and proteins
• Avoid affecting receptor binding affinity or in vitro biological activity
• Improved in vivo efficacy
• Increase the half-life to varying degrees

Creative Biolabs has been a long-term expert in the field of drug development. As a pioneer and the undisrupted global leader in half-life extension, we offer a variety of solutions to improve your productivity and streamline your research processes. If you are interested in our products or services, please do not hesitate to contact us for more detailed information.

Reference

1. Tan, H.; et al. Recent advances in half-life extension strategies for therapeutic peptides and proteins. Current pharmaceutical design. 2018, 24(41): 4932-4946.