Peptide Synthesis
Peptide synthesis is the assembly of a defined amino-acid sequence into a molecule that can be purified, characterised and released against a specification. This hub collects our technical guides on solid-phase and liquid-phase chemistry, difficult sequences, scale-up and the documentation that should accompany every batch.
How custom peptide synthesis works
Most custom peptides are built by solid-phase peptide synthesis (SPPS): the C-terminal amino acid is anchored to a resin, then cycles of deprotection and coupling add one residue at a time. After chain assembly the peptide is cleaved from the resin and the side-chain protecting groups are removed, usually with trifluoroacetic acid in the presence of scavengers. Crude peptide is then purified by preparative reverse-phase HPLC and released with an HPLC purity value, a mass-spectrometry identity check and a certificate of analysis.
SPPS versus LPPS: choosing the method
SPPS is the default for sequences up to roughly 50 residues and for projects that need rapid iteration. Liquid-phase peptide synthesis (LPPS) becomes attractive when the sequence is short, when very large amounts of a protected fragment are needed, or when the product must avoid resin-derived impurities. Hybrid routes fragment the sequence, make each fragment by SPPS and join them in solution. The right choice depends on length, hydrophobicity, scale and the purity target rather than on a fixed rule.
Sequence feasibility and difficult sequences
Hydrophobic stretches, repeated beta-sheet motifs, multiple cysteines and sequences rich in arginine are the usual causes of incomplete coupling or aggregation on resin. A feasibility review looks at the sequence, the intended C-terminal modification, disulfide pairing and solubility before a quote is issued. Where risk is high, the pragmatic options are pseudoproline dipeptides, microwave-assisted coupling, a switch to a fragment strategy, or an adjusted purification method.
Scale, purity grades and release testing
Custom work at MOL Changes runs from milligram screening lots to kilogram-scale campaigns. Purity is agreed before synthesis rather than chosen after purification, because the achievable gradient depends on the sequence. Standard release testing combines analytical HPLC, electrospray mass spectrometry and, where requested, MS/MS fragmentation, amino-acid analysis or net-peptide-content determination. Every result is tied to the batch number printed on the certificate of analysis.
What to send in a synthesis enquiry
A useful enquiry contains the sequence or a description of the target, the N- and C-terminal modifications, any non-natural residues, the required quantity, the purity target, the delivery form (lyophilised powder or solution) and any documentation requirements. Counter-ion, salt form and solubility constraints should be stated up front because they influence both purification and the final specification.
Articles in this topic
- Custom Glycopeptide Synthesis — Specify and Assess Structural Heterogeneity
- A Positive Labeled-Peptide Signal — Controls for Competing Explanations
- Neoantigen Peptide Pools — Member Identity, Amount and Batch Traceability
- Antibody Production with Synthetic Peptides — Controls for Peptide and Protein Recognition
- Antimicrobial Peptide Synthesis — Choose and Interpret the Assay Context
- Peptide Purification Services — Write a Brief for Purity and Usable Recovery
- Custom Peptide Analytical Services — Choose Methods by the Decision They Support
- Peptide Shipping Excursions — Record the Exposure Before Deciding Suitability
- Dissolving Peptides — Distinguish Clarity, Recovery and Monomeric State
- Custom Peptide Expiration and Retest Dates — Five Evidence Misconceptions
- Dual-Supplier Peptide Sourcing — Build a Common Comparability Assessment
- Research Peptide Lot Bridging — Five Misconceptions About Replacement Material
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Frequently asked questions
What is the longest peptide you can synthesise?
Routine solid-phase work covers sequences up to about 50 residues. Longer targets are handled by fragment condensation or hybrid routes after a feasibility review, because yield and purity fall sharply as chain length and hydrophobicity increase.
Can you synthesise a peptide from a sequence I provide?
Yes. Send the sequence with the required N- and C-terminal modifications, quantity, purity target and delivery form. We review feasibility, flag risky motifs and return a quotation with the proposed method and lead time.
What purity can I expect?
Purity is agreed per project. Crude screening lots are typically below 70 percent by HPLC; standard purified lots are 95 percent or higher, and higher purity is available for sequences that can be separated cleanly on a preparative gradient.
Do you supply a certificate of analysis with each batch?
Every released batch is accompanied by a certificate of analysis that records the batch number, sequence, appearance, HPLC purity and mass-spectrometry identity, together with the analytical method used for release.
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