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Stapled Peptide Development Services

Protein-protein interactions (PPIs) are one of the key mechanisms underlying numerous signaling pathways in the body and are also a root cause of many intractable diseases. In recent years, PPI targets have become a research hotspot in the development of targeted therapies for cancers, autoimmune diseases, and other conditions. Because protein-protein interaction interfaces are large and disease treatment requires drugs to have good cellular permeability, small-molecule drugs and macromolecular proteins face limitations in terms of targeting specificity and intracellular targeting, rendering many PPI targets “undruggable.” Peptides have a small molecular weight, low immunogenicity, and the ability to target both intracellular and extracellular proteins, while also matching the size of macromolecular protein-binding interfaces. However, natural peptides (especially those with α-helix structures) are easily degraded by proteases in vivo, exhibit poor metabolic stability, and are structurally unstable. They are prone to losing their target protein-binding activity, leading to off-target effects and hindering efficient crossing of the cell membrane to reach the target site. Therefore, stabilizing the secondary structure of natural peptides (such as α-helices) facilitates the development of drugs for the specific targeting of PPI targets, which is of great significance for the treatment of intractable diseases such as cancer and autoimmune diseases.

The development of stapled peptides has broken through the “undruggable” barrier associated with PPI targets. Stapled peptides utilize either the “all-carbon chain” stapling method (i.e., an all-carbon backbone) or the “side-chain-selective” stapling method to form side-chain cyclization structures that modify peptides, thereby stabilizing the active conformation of α-helical peptides. Peptides obtained through this method, which uses an all-carbon backbone as a scaffold to stabilize the α-helical structure of the peptide, are referred to as stapled peptides (Stapled Peptide). Stapled peptides are designed to enable peptide drugs to stably, efficiently, and specifically target PPI targets both inside and outside cells (the stable α-helix structure enhances the metabolic stability of the targeting peptide, making it less susceptible to proteolytic degradation; it also increases binding activity to protein surfaces, resulting in higher affinity, better targeting; furthermore, the amphiphilic nature of the α-helix mimics the characteristics of cell-penetrating peptides, resulting in improved cell permeability), thereby addressing the challenge of “undruggability.” At the same time, the development of stapled peptides also facilitates the development of high-quality peptide-drug conjugates (PDCs).

Figure 1- Schematic Diagram of the Design Principle of a Stapled Peptide.png

Figure 1: Schematic Diagram of the Design Principle of a Stapled Peptide

Leveraging its extensive experience in targeted peptide development and an integrated peptide drug development platform (including target design, peptide screening, stapled peptide design and synthesis, affinity detection, in vitro drugability evaluation, and in vivo efficacy evaluation in animals), TekBiotech provides comprehensive services ranging from preclinical study design, targeted peptide discovery, stapled peptide development, to downstream detection and efficacy evaluation. TekBiotech focuses on overcoming key challenges in stapled peptide development—specifically, the stability of α-helix structures (which directly affect a peptide’s surface binding activity, affinity, target specificity, metabolic stability, and cellular permeability)—to accelerate the development of drug candidates and advance them from the laboratory to clinical trials.

█ Stapled Peptide Development Services

TekBiotech offers a standardized stapled peptide development process. TekBiotech’s scientists will design customized screening strategies based on the customer-provided target information (primarily PPIs) to generate specific targeting peptides for downstream stapled peptide development and application. The stapled peptide development service covers a full suite of development services, including screening target design and production, targeted peptide screening, stapled peptide design and synthesis, affinity detection, in vitro efficacy evaluation, and in vivo efficacy evaluation in animals.

TekBiotech offers two design approaches: the “all-hydrocarbon chain” synthesis method (i.e., an all-carbon backbone) and the “side-chain-selective” synthesis methods. Typically, peptides are approximately 2–3 helix lengths (or 8–12 amino acid residues) in length. TekBiotech’s scientists design and synthesize peptides based on the amino acid characteristics of the target peptide sequence (for example, forming cross-links between side-chain groups at positions i and i+4 or i and i+7 to stabilize the α-helix conformation).

Methods for the Synthesis of Stapled Peptides	Quality Control Methods	Activity Detection
“All-hydrocarbon chain” synthesis method (i.e., the All-hydrocarbon chain RCM reaction (ring-closing metathesis reaction of olefins) method)	HPLC and MS detection	Affinity detection, cell-level detection, and efficacy evaluation in Animal Models
“Side-chain-selective” synthesis methods (α-keto-aldehyde method, diisocyanate method, etc.)	HPLC and MS detection	Affinity detection, cell-level detection, and efficacy evaluation in Animal Models

█ Advantages of the Stapled Peptide Development Service Platform


One-Stop Solution	Customized Solutions	Strict Quality Control	Mature Platforms that Support Downstream Detection
Comprehensive services ranging from scheme design, targeted peptide discovery, and the design and synthesis of stapled peptides to in vivo and in vitro detection	A variety of synthesis methods for stapled peptides are available	HPLC and MS detection	Affinity detection, cell-level detection, in vivo targeting detection, and efficacy evaluation