For Research Use Only. Not for Clinical Use.

Creative Biolabs has long-lasting expertise in the design and conduct of novel drug molecules. Based on our advanced platforms and extensive experience, now we can provide ELPylation-based half-life extension services for our clients all over the world.

Introduction of ELPylation

Elastin-like polypeptides (ELPs) are a class of stimulus-responsive biomaterials for controlled drug delivery. ELPs are composed of short repeating peptide motifs containing VPGXP, where X is a guest residue that can be any amino acid except proline. As a stimulus-responsive biomaterial, ELPs are completely dissolved in an aqueous solution below the reverse transition temperature (T_t) and aggregate into a micron-sized coacervate at a temperature above T_t. This phase change is reversible and can be completed in a short time, that is, when the ELP coacervate returns to a temperature below T_t, it will re-dissolve. What’s more interesting is that the T_t of ELPs can be adjusted by changing the guest residues and the length of the ELPs.

Factors Affecting T_t of ELPs

• The amino acid composition of ELP: Hydrophobic guest residues will decrease T_t, and hydrophilic guest residues will increase T_t.
• The molecular weight (MW): An increase in MW leads to a decrease in T_t.
• Concentration and solutes: An increase in ELP concentration causes a decrease in T_t.
• Solution pH
• Cosolutes, such as salts: Ionophilic salt inhibits ELP T_t.

Fig 1. Intrinsic design parameters of ELP length and guest residue composition provided precise control of the T_t. (MacEwan, 2014)

Applications of ELPylation in Half-Life Extension

ELP is biocompatible, so it will not cause adverse immune reactions when applied to the human body. In this case, ELP polymers have been widely applied in therapeutic peptides or proteins to control the half-lives and bioavailability. For example, ELPylation GLP-1 analog expressed in E.coli has been used as a once-weekly treatment for type 2 diabetes mellitus. The polymer formed by the fusion of vasoactive intestinal peptide (VIP) and ELP is highly resistant to enzymatic degradation and the half-life in the human body is increased to 60 hours. Natural insulin molecule fused with ELP polymer gene is used as a once-weekly treatment against diabetes-related hyperglycemia.

Advantages of ELPylation in Half-Life Extension

• ELP is biocompatible and causes minimal inflammation and immunity.
• The genetic coding design of ELP allows precise control of the sequence of ELP.
• ELP can be safely biodegraded and easily removed from the body.

Based on long-term expert in the field of drug development, Creative Biolabs provides a variety of solutions to fit your specific research needs. If you are interested in our products or services, please do not hesitate to contact us for more detailed information.

Reference

1. MacEwan, S.; Chilkoti, A. Applications of elastin-like polypeptides in drug delivery. Journal of Controlled Release. 2014, 190: 314-330.