Disulfide-Rich Peptide (DSR) Synthesis

Disulfide-rich peptides, a class of peptides linked by two or more disulfide bonds, have emerged as promising therapeutic and diagnostic agents, especially in the treatment of metabolic and digestive diseases. Thanks to decades of hands-on experience in peptide synthesis and research, CD Formulation has developed a robust synthesis procedure that is suitable for most DSRs. Our extensive expertise allows us to provide the highest quality and purity for individual topoisomers of DSR.

What is Disulfide-Rich Peptide (DSR)?

DSRs are a class of peptides characterized by the presence of multiple disulfide bonds, which are covalent bonds formed between cysteine residues. These disulfide bonds contribute to the structural stability and bioactivity of peptides, allowing them to maintain their functional conformation in a variety of environments, including harsh conditions such as high temperature or extreme pH. Advantages of DSRs include:

• Improved stability of peptide drug leads.
• Enhanced conformational rigidity.
• Facilitated delivery to intracellular targets.
• Not susceptible to enzymatic degradation.
• Strong binding affinity to corresponding receptors.

Although natural DSRs have been widely used to develop protein binders or potential therapeutics, their synthesis and redesign to bind new targets are not straightforward due to the difficulty in dealing with disulfide pairing issues. Rationally designed DSRs with intrinsic orthogonal disulfide pairing propensity provide an alternative to natural scaffolds for developing functional DSRs.

Fig. 1 Sequences and structures of three disulfide-rich peptide families. (Northfield SE, et al., 2014)

Explore Our Custom Disulfide-Rich Peptide (DSR) Synthesis Services

At CD Formulation, our team of peptide synthesis experts has the expertise and specific skills to design and synthesize high-quality DSRs for a variety of applications based on your needs.

Our scientists are familiar with a variety of synthesis techniques, including solid-phase peptide synthesis (SPPS), liquid-phase peptide synthesis (LPPS), and chemo-enzymatic peptide synthesis (CEPS), allowing us to select the most appropriate technology to support each individual peptide synthesis project. At the same time, we strictly follow quality control standards to ensure that we provide you with high-purity, low-impurity peptide products.

Our scientists have thoroughly studied existing procedures and protecting group techniques for DSR syntheses, improved and optimized them, and developed a set of in-house general conditions applicable to all DSR syntheses.

Our services include but are not limited to the following:

• Synthesis of peptides with intrachain disulfide bonds.
• Synthesis of peptides with interchain disulfide bonds.
• Synthesis of peptides with five or more disulfide bonds.
• Synthesis of long peptides with intrachain disulfide bonds.
• Synthesis of peptides with heterodisulfide bonds.
• Synthesis of peptides with disulfide bonds combined with stable isotopes or fluorescent labels.

Our Synthesis Strategies for Disulfide-Rich Peptide (DSR)

Orthogonal Disulfide Pairing Motif

Orthogonal disulfide pairing motifs generally refer to the use of two different sets of cysteine residues in a particular peptide design to form non-interfering disulfide bonds, thereby achieving a specific structure or function of the peptide.

Our peptide synthesis team uses tandem cysteine-any residue-amine motifs to direct the oxidative folding of peptides and has successfully synthesized a variety of DSRs using various cysteine/amine residue patterns and incorporating tandem motifs into peptides.

Orthogonal Protecting Group Strategies

In order to synthesize DRPs that can express the correct biological functions, our scientists have conducted various orthogonal protecting group strategies to ensure the correct connection between cysteines.

With long-term experience in DRP synthesis, we have applied and optimized a variety of cysteine protecting groups, which allows for simple and rapid synthesis of DSRs containing different SS bonds.

Fig. 2 Synthesis of cyclic disulfide-rich peptides by Fmoc-SPPS and Boc-SPPS approaches. (Akcan M, et al., 2013)

Molecular Grafting

Molecular grafting is a technique that connects specific molecules or polymer chains to the surface of materials or other molecules through chemical reactions. This technique is an effective way to stabilize and confine peptides and involves fusing bioactive peptide sequences to suitable molecular scaffolds. It can improve the stability of bioactive peptide leads and potentially expand their functions.

Our peptide experts have established a powerful molecular grafting process to improve the stability of disulfide-rich peptide drug leads by enhancing conformational rigidity.

Peptide Manufacturing & Analytical Services

In addition to peptide synthesis capabilities, CD Formulation combines flexible GMP manufacturing facilities with cutting-edge peptide analytical knowledge to provide a full range of quality control testing services to accelerate the commercialization of your products, including:

Publication

CD Formulation's DSR synthesis services are tailored to meet the specific needs of researchers and organizations seeking high-quality peptides for drug discovery, vaccine development, diagnostics, and other scientific endeavors. Please don't hesitate to contact us if you are interested in our services. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.