For Research Use Only. Not for Clinical Use.

Inducing monomer's self-assembly to form protein polymers by chemical modification is commonly used to prolong the half-life of therapeutic proteins or peptides. Bipyridine modification takes advantage of the complexation ability of bipyridine group and Fe²⁺ ions to form a trimerization domain with Fe²⁺ as the core, thus improving the pharmacokinetic properties. This unique technology can be widely used in a variety of protein drugs. As a leading service provider in the therapeutic protein area, Creative Biolabs keeps up with the time and launches bipyridyl based half-life extension service. Our highly experienced staff can offer professional and meticulous service to accelerate your drug research process.

Fig.1 Native and engineered insulin oligomers. (Munch, 2011)

Introduction of Bipyridy Based Half-Life Extension Service

Compared with the lipophilic group mediated protein self-assembly, the mechanism of bipyridine modification is very special. Bipyridine has a high affinity for Fe²⁺ in vitro and forms a chiral tris-bipyridyl Fe²⁺ complex, which can make protein drugs more stable in the delivery process by free from endogenous enzyme degradation, thus raising the pharmacokinetic properties of therapeutic proteins. Although the Fe²⁺ based oligomer is reversible, it remains stable in the change of microenvironment in vivo. Moreover, because of the tiny format bipyridine group, it will not harm the recognition of the protein to the receptor, which maintains its potency. Moreover, bipyridyl based half-life extension technology has the distinguishing advantage of forming only homogeneous trimers, which contributes to the production of the drug under Good Manufacture Practice standards. Because of various advantages, bipyridyl based half-life extension is a promising new method and is widely used in drug research.

Applications of Perfluoroalkylation Based Half-Life Extension Service

In the early studies, bipyridine modification was mainly used to prepare multivalent small molecule drugs. Nowadays, this strategy has been gradually applied in the modification of therapeutic proteins. Actually, certain well-defined noncovalent protein oligomers are steadily assembled by metal ions under physiological conditions, which suggests that Metal ion mediated protein self-assembly is an available method to prolong drug half-life. The most typical study is that bipyridine modified insulin obtains a strong sustained release effect through Fe²⁺ complexation of trimer and prolongs the half-life. More surprisingly, owing to the fact that insulin can conjugate with Zn²⁺ in vivo leads to the cross-linking of insulin through Fe²⁺ and Zn²⁺ and eventually constructs high poly nanoassemblies, which further improve its half-life and potency. This result demonstrates the feasibility of bipyridyl based half-life extension, and further optimization of the structure of bipyridine derivatives group can theoretically extend the half-life of pharmaceutical proteins.

Fig.2 Molecular model and 2D representation of a HI–bipy 54-mer. (Munch, 2016)

Highlights of Bipyridy Based Half-Life Extension Service

• Novelly, inexpensively, and conveniently.
• Widely suitable for most protein drugs.
• Homogenous polymeric therapeutic proteins are produced.
• The derivative group is small and does not affect the natural folding configuration.

Bipyridyl based half-life extension is commonly used in various drugs development owing to its low-cost and convenience. Please feel free to contact us for more information.

References

1. Munch, H. K.; et al. Controlled sell-assembly of re-engineered insulin by FeII. Chemistry-a European Journal. 2011, 17(26), 7198-7204.
2. Munch, H. K.; et al. Construction of insulin 18-mer nanoassemblies driven by coordination to iron (II) and zinc (II) ions at distinct sites. Angewandte Chemie International Edition. 2016, 55(7), 2378-2381.