Peptide Linker Design

As a specialist in biomedical related technical services, Creative Peptides is able to design a wide variety of peptide linker for customers in a high-yield and cost-effective way of best quality, ensuring the expected stability of peptide junctions and providing better drug release control.

Introduction

In general, Linker is designed to be stable in the blood environment, while payload can be rapidly degraded and released in lysosomes or tumor microenvironments. At the same time, it also requires that linker should maintain good stability in buffer solution so as to facilitate storage and transportation. The cleavage of peptide bond depends on lysosomal protein hydrolase, whose activity in blood is very low. Therefore, peptide bond has excellent serum stability. Peptide linker, as a kind of restriction enzyme-digested linker, has high stability in blood and cleavage quickly in lysosome, so it is widely used.

Application of peptide linkers

• ADC (Antibody-Drug Conjugate)

In the design and development of ADC, linker, which connects payload and antibody, has an important influence on the efficacy of ADC. Its structural design and chemical properties are directly related to the stability, safety and specificity of ADC drugs. According to the mechanism of payload release, Linker can be divided into cuttable and uncuttable types. As a kind of Linker- digested by restriction enzyme, peptide linker has the characteristics of high stability in blood and fast cleavage in lysosome, so it has been widely used in ADC development. In recent years, the most widely used peptide junctions are Val-Cit and Phe-Lys, which are optimized dipeptide-based junctions that can be cleaved by lysosomal extracts and purified human cathepsin B.

• Fusion Protein Linkers

As a helical joint, peptide linker can improve the folding and stability of the fusion protein. For example, in the development of virus coat protein fusion protein, only peptides of less than 20 amino acids can reach the coat protein of plant rod virus without preventing the assembly of functional virions.

• PROTAC (Proteolysis targeting chimeric)

PROTACs constructed by using peptides as linker has the advantages of high specificity and low toxicity, and avoids the limitation of shallow binding pockets formed by large interaction surfaces, which provides a reliable solution for ubiquitination of “undruggable protein” mediated by E3 ubiquitin ligase complex.

• Control of protein functional dynamics

Controlling structural flexibility is essential for the normal operation of a large number of protein and polyprotein complexes. Joints are considered to control the favorable and unfavorable interactions between adjacent domains through the variable softness provided by their first-order sequences. The large-scale structural heterogeneity of multi-domain proteins and their complexes is promoted by soft peptide junctions. At the residue level, this flexibility is due to the local relaxation of peptide bond angles, and its cumulative effect may lead to great changes in the secondary, tertiary or fourth-order structure of protein molecules.

Our services

Peptides are complex biomolecules with unique chemical and physical properties, which is the direct result of their amino acid composition. According to the application that the customer needs, we can design peptide linker from scratch or design peptide linker based on natural protein peptide sequence. Synthetic peptides can be modified to change their properties or conformation.

Following is our products: