Long Peptide Synthesis | Long Chain Peptide Customization | Difficult Peptide Synthesis | Peptides over 50mer | Science-Peptide
Meta Description
Need a long peptide with more than 50 amino acids? Science-Peptide's Long Peptide Synthesis service covers 50-189 amino acids, with a segmented synthesis strategy, overcoming the problems of hydrophobic aggregation and low synthesis efficiency, etc. 20 years of experience and stable delivery. Welcome to contact us.
Long Peptides: The Longer They Are, The More Trouble They Cause
Why are long peptides hard to make?
Anyone who has done peptide synthesis knows that the problem arises when the peptide chain is long: within 20 amino acids, most companies can do it. When it comes to more than 40 amino acids, we start to pick the sequence. At 60 amino acids or more, the number of companies that can take over is reduced by half. When it comes to over 100 amino acids, there are not many companies that dare to do it.
Why? Because Long Peptide Synthesis encounters several pitfalls:
Synthesis efficiency decreases: each extension of an amino acid, the yield will be discounted once. 30 amino acid peptide, each step of 99% yield, the final yield is still 74%; 60 amino acids, each step is still 99%, the final yield is only 55%. In fact, the yield of many steps can not reach 99%.
Hydrophobic aggregation: When there are a lot of hydrophobic amino acids in a long peptide, the peptide chain starts to "clump" on the resin, and the amino acids behind it cannot enter.
Difficulty in purification: the retention time of long peptides and impurities are too close to each other for a clean cut.
Poor solubility: When the peptide is obtained, it cannot be dissolved, so the experiment cannot be done.
We've been in these potholes before, and we know how to get around them.

What We Can Do
1. Length: 50-189 Amino Acids
|
length range |
Difficulty |
We've done situations where |
|
50-80 aa |
Upper middle class |
Routine program with >90% success rate |
|
80-120 aa |
High |
Need segmented synthesis strategy, enough experience |
|
120-150 aa |
Very high |
I've done a lot of them, up to 150. |
|
150-189 aa |
Extremely high |
Challenge level, with success stories |
2. Segmented synthesis strategy
The most effective way to deal with long peptides is to segment them:
Segment selection: Cut the long peptide into 2-4 segments of 30-60 amino acids each. The cut point should be located at the position where the synthesis difficulty is low, for example, avoiding the continuous hydrophobic region.
Fragment synthesis: Each fragment is synthesized and purified individually to a sufficiently high purity.
Fragment splicing: joining fragments together in solution or on a resin. The joining method can be either natural chemical or enzymatic.
Folding: If the peptide has a disulfide bond, it must be folded into the correct conformation after splicing.
3. Purity: Depending on Experimental Requirements
|
Purity level |
Applicable Scenarios |
|
Conventional pure (85-95%) |
Combining experimental, active primary screening |
|
High purity (95-98%) |
cellular experiments, functional validation |
|
Ultrapure (>98%) |
Structural studies, crystallography |
Each long peptide is accompanied by an HPLC and MS report, making the purity data transparent.
4. Modifications: long peptides can also add function
Fluorescent labeling: FITC, TAMRA, want to see where the long peptide runs.
Biotin:Do pull-down or test.
Isotope labeling: for NMR or mass spectrometry quantification.
Phosphorylation/glycosylation: mimicking post-translational modifications.
Why Come To Us For Long Peptide Synthesis?
1. We've been doing this for 20 years
Long Peptide Synthesis is not something that anyone can do. Over the years, we have handled a lot of long peptides: transmembrane protein fragments, viral fusion peptides, amyloid proteins, antimicrobial peptides, etc. We have a good idea of which sequences are easy to aggregate and which conditions can save them. If you come to us for Long Peptide Synthesis, at least you don't have to step on the pit from the beginning.
2. Fractional synthesis: not just cutting into pieces
Segmentation sounds simple, but where to cut, how long each segment is, and how to connect them are all important. We have several principles:
Cut in the hydrophilic zone: Avoid cutting in the hydrophobic core, otherwise the segments will gather by themselves.
Balance the length of the fragments: Don't make one segment particularly difficult to do and other segments particularly easy. 3.
Connection point selection: Natural chemical connections require a thioester at the C-terminal and Cys at the N-terminal, which must be designed in advance.
3. Hydrophobic peptides: special solvent system.
Some long peptides are so hydrophobic that they cannot be solved by conventional solvents, so they will be clumped together on the resin when synthesized. We have a special solvent system and additives to keep the peptide chain stretching during the synthesis process, so that the following amino acids can enter.
4. Quality control: data at every step
Quality control of long peptides is more complex than that of short peptides:
Quality control of intermediates: after synthesizing each fragment, measure the purity and molecular weight first, and then go on to the next step after passing the test.
Splicing process monitoring: Sample the connection reaction and measure the MS to see the connection efficiency.
End product inspection: HPLC for purity, MS for molecular weight, MS/MS for sequence correctness (optional).
Solubility test: Provide recommended solvents and solubilization methods, so that you do not get peptides that do not dissolve.
Doing Long Peptide Synthesis, the data speaks for itself and every step is traceable.
5. From milligrams to hundred milligrams, all the way to the end
Milligrams for the screening phase, ten milligrams for the validation phase, a hundred milligrams for the structural study - we can take it all. The same project, the same counterpart, no need to re-harmonize.
What Can Long Peptides Be Used For?
|
Research areas |
Common Uses |
We've done situations where |
|
Membrane proteins |
transmembrane fragments, extracellular loops |
Long peptide with multiple transmembrane regions, highly hydrophobic |
|
Viral proteins |
Fusion peptides, receptor-binding domains |
New coronavirus S protein fragment, around 100aa |
|
Amyloid |
Aβ, α-synuclein |
42aa is the norm. Longer ones have been done |
|
Antimicrobial Peptides |
Long-chain antimicrobial peptides |
Some natural antimicrobial peptides are just 40-60aa |
|
Cytokines |
simulating the active zone |
50-80aa, with disulfide bonds |
|
Structural biology |
NMR, crystallography |
Isotopically labeled peptide, purity >98%. |
Delivery and quality control
- Delivery: Lyophilized powder, centrifuge tubes or vials, protected by nitrogen.
- Accompanying documents:COA (HPLC profile + MS profile), MS/MS (sequence confirmation optional), synthesis report (segmentation and splicing process).
- Optional tests: peptide content, endotoxin, moisture, amino acid composition, solubility test.
- Customized Packaging: portioning and marking according to your requirements.
- Each Long Peptide Synthesis product is double-checked to ensure that the sequence is correct and the purity is up to standard before it is sent out.



Three Real-life Cases
Case 1: Membrane protein program at a research institute
The customer needs a 85aa transmembrane peptide for structural study. This peptide has 60% of hydrophobic amino acids, so many companies could not make it. We used segmental synthesis, cut into three segments, each segment is about 30aa, purified and then liquid-phase ligated. The final purity of the peptide is >95%, and the customer got it and did NMR.
Case 2: Viral protein program of a multinational pharmaceutical company
A 110aa viral fusion peptide with two pairs of disulfide bonds was required for inhibitor screening. We designed a segmented synthesis strategy to synthesize three linear fragments first, which were joined and then oxidized to form disulfide bonds. The final product was delivered with >90% purity, correctly paired disulfide bonds, and passed the activity verification.
Case 3: Amyloid research at a national university
The customer needs a 70aa fragment of alpha-synuclein for the study of aggregation mechanism. This peptide is easy to form fibers and always blocked the column during purification. We optimized the mobile phase conditions, added a small amount of organic solvent, and finally obtained a product with purity >95%, and the customer successfully performed ThT experiments.
Talking About Your Long Peptide Needs?
Whether you want an 80aa transmembrane peptide or a 150aa viral protein, you can talk to us. If you ask Science-Peptide to do Long Peptide Synthesis, at least you don't have to try one by one.
I need you to tell me:
Peptide sequence (or target information)
How much (milligrams)
PurityPurity ements
Have no Have fide bonds or other modifications
When do you want it?
Give you a feasibility assessment and quote within 24 hours.