Cyclic Peptide Synthesis | Custom Cyclic Peptides | Stapled Peptides | Side Chain Cyclization | Science-Peptide
Meta Description
Need difficult cyclic peptides? Science-Peptide's Cyclic Peptide Synthesis service covers first and last cyclization, side chain cyclization, stapled peptide, multiple disulfide bond pairing. 20 years of experience in complex cyclic peptides, stable delivery. Please feel free to contact us.
Cyclic peptide: an upgraded version of the linear peptide
Why Cyclic Peptides?
Anyone who has worked with peptides knows that linear peptides work well, but sometimes they don't work so well - they are cleaved by enzymes within a short time of entering the body, or they don't bind tightly enough to the target site. Making linear peptides into loops is the most direct way to solve these problems.
Cyclic peptides have a more fixed conformation and are not easy to be cut by proteases; when they are combined with the target, because the structure has been locked, the loss of entropy is small, and the binding force is stronger. Many natural active peptides are cyclic in nature, such as antibacterial peptides and immunosuppressants, for which evolution has long chosen the direction for us.
However, the difficulty of Cyclic Peptide Synthesis is indeed much higher than that of linear peptides. We have stepped on these potholes before, and we know how to get around them, such as the low efficiency of ring formation, many side reactions, and the impossibility to recover the purification.

What can we do about ringing?
1. Circularization: Depending on What You Want
|
Cyclization type |
How to |
When to use it |
|
First and last annularization |
N-end and C-end are directly connected |
Mimicking natural cyclic peptides, short peptides are commonly used |
|
side-chain cyclization |
cyclization through Lys, Glu, and Asp side chains |
You want to leave the end for trim, or the ring is bigger |
|
disulfide bond cyclization |
The formation of a disulfide bond between Cys |
Antimicrobial peptides, toxin peptides, most naturally occurring |
|
Stapled peptides |
The hydrocarbon chain pins the helix |
Stabilization of the alpha-helix and enhancement of membrane penetration |
|
Sulfur ether cyclization |
Non-natural bonding, more resistant to enzymatic degradation |
To be made into a drug, it requires high metabolic stability |
Depending on your target structure, we will determine which cyclization is most appropriate. The first step in Cyclic Peptide Synthesis is to choose the right cyclization method.
2. Disulfide bonds: one to four pairs have been done
Single pair disulfide bond: routine operation, success rate over 95%.
Two pairs of disulfide bonds: need to control the order of pairing, we have orthogonal protection strategy.
Three or more pairs: Up to four pairs, opened and matched one by one.
3. Length: 2-60 amino acids after cyclization
The longer the cyclic peptide, the better, the longer the cyclization efficiency will be down. The longest cyclic peptide we have ever made is 60 amino acids, and we synthesized the linear fragment in segments first, and then cyclized it in liquid phase.
4. Purity: depending on the experimental stage
|
Purity level |
Appropriate scenarios |
|
Crude (70-85%) |
Initial screening, see if it's active first, save money |
|
Conventional pure (85-95%) |
Cellular experiments, combined with experiments that |
|
High purity (95-98%) |
Animal experiments, functional validation |
|
Ultrapure (>98%) |
Crystal structure, NMR |
Each cyclic peptide is accompanied by HPLC and MS reports, and the cyclization efficiency, residual linear peptide, and purity are clearly labeled.
5. The ring can also be modified
Fluorescent labeling: FITC, TAMRA, Cy5, want to see where the cyclic peptide goes.
Biotin:Do pull-down or test.
PEGylation:Prolongation of in vivo half-life.
D-type amino acids:Improve stability.
Why come to us for Cyclic Peptide Synthesis?
1. We've been doing this job for 20 years
Cyclic Peptide Synthesis is not just a matter of throwing a linear peptide into a reaction vial and stirring it up. If the cyclization conditions are a little bit off, either the yield will be so low that you will doubt your life, or there will be a lot of by-products that can't be separated.
Cyclization of transmembrane peptides, conotoxin with three pairs of disulfide bonds, stapled helical peptides - we have handled a lot of difficult cyclization peptides over the years. We have a good idea of which sequences are easy to polymerize and which conditions can save them. If you come to us for Cyclic Peptide Synthesis, at least you don't have to step on the pit from the beginning.
2. Cyclization strategies: solid phase or liquid phase, the choice is yours
Solid-phase cyclization: direct ring formation on resin, suitable for short peptides and side chain cyclization, easy to operate, suitable for high throughput.
Liquid phase cyclization: purification of linear peptides followed by cyclization, suitable for long peptides or when dilute conditions are required to avoid polymerization.
Two-step method: solid-phase synthesis of linear peptide, purification, and then liquid-phase cyclization to balance the purity and yield.
There's no one-size-fits-all approach. We'll pick the most reliable route based on your sequence and cyclization method.
3. Disulfide bond matching: no guessing, no strategy
The most difficult thing about multiple pairs of disulfide bonds is the pairing order. We have an orthogonal protection strategy, which can open and pair them one by one to ensure that the disulfide bonds are connected in the right place.
4. Quality control: each cyclic peptide is documented
MS: First, see if the molecular weight is correct (18 or more less than linear after cyclization, depending on the method of ring formation).
HPLC: look at the purity, and also look at how many linear peptides are not looped.
Optional: peptide content, endotoxin, moisture.
Doing Cyclic Peptide Synthesis, the data speaks for itself, no falsehoods.
5. From small to large quantities, without changing suppliers
Milligrams in the screening phase, ten milligrams in the validation phase, a hundred milligrams to grams in the preclinical phase - we can do it all. The same project, the same counterpart, no need to re-harmonize.
What Can Cyclic Peptides Be Used For?
|
Research directions |
Common Uses |
Cyclization approach |
|
Antimicrobial peptides |
Improved stability, less susceptible to enzymatic cleavage |
disulfide bond cyclization, head-to-tail cyclization |
|
Antitumor peptides |
Enhanced binding to the target |
stapled peptides, side chain cyclization |
|
immunosuppression |
cyclosporine analogs |
First and last annularization |
|
cell-penetrating peptides |
Improving the ability to enter cells that |
Stapled peptides |
|
toxin research |
Conotoxin, snake venom peptides |
Multiple pairs of disulfide bonds |
|
peptide hormones |
prolonged half-life |
side-chain cyclization |
|
diagnostic reagents |
Ring probe, good specificity |
may be labeled with biotin or fluorescent markers |
Delivery and quality control
- Delivery: Lyophilized powder, centrifuge tubes or vials, protected by nitrogen.
- Accompanying documents:COA (HPLC profile + MS spectrum), MS/MS (to confirm cyclization site/disulfide bond pairing).
- Optional tests: peptide content, endotoxin, moisture, amino acid composition.
- Customized Packaging: portioning and marking according to your requirements.
- Each Cyclic Peptide Synthesis product is double-checked to ensure correct cyclization and purity before shipment.



Three true stories
Case 1: Antimicrobial peptide program of a research institute
The client wanted a cyclic peptide containing two pairs of disulfide bonds, 28 amino acids, of natural origin. We designed an orthogonal protection strategy, forming the first pair first, then oxidizing to form the second pair. Finally, the purity of the cyclic peptide is >95%, the disulfide bonds are correctly paired, and the activity is verified.
Case 2: The stapled peptide project of a multinational pharmaceutical company
The customer wanted a stapled peptide with stabilized α-helix and 22 amino acids. We introduced olefinic amino acids into the solid-phase synthesis and completed the ring closure on the resin. The purity was >90% and the helix was 40% higher than that of the linear peptide, and the peptide was successfully introduced into animal experiments.
Case 3: Toxin research at a national university
The customer wanted to make a Conotoxin containing three pairs of disulfide bonds, and asked several companies to make it. We redesigned the protection strategy, opened and paired the disulfide bonds in three steps, and confirmed the correct pairing by MS/MS. After the customer got the peptide, we solved the structure and published the article.
Talking about your cyclic peptide needs?
Whether you want a difficult cyclic peptide for critical experiments, or you want to cyclize a linear peptide to improve the drugability, you can talk to us. If you are looking for Science-Peptide to do Cyclic Peptide Synthesis, at least you don't have to step on the pit from the beginning.
I need you to tell me:
Peptide sequences (or linear sequences)
How do you want to cyclize (first and last/side chain/disulfide bond/stapled peptide)
How much to ask for (mg/g)
purity requirements
When do you want it?
Give you a feasibility assessment and quote within 24 hours.