How Long Peptides Are Produced

Standard SPPS starts struggling around 40-50 amino acids. Beyond that, you need different approaches.

Why Long Sequences Are Hard

Incomplete couplings accumulate with each cycle. Aggregation on resin blocks further amino acid addition. Even at 99.5% coupling efficiency per step, a 50-mer has a theoretical full-length yield under 80%.

Fragment Condensation

Synthesize two or more shorter fragments, then couple them in solution. Each fragment is easier to purify individually. The ligation step requires orthogonal protecting groups.

Native Chemical Ligation

A C-terminal thioester on one fragment reacts with an N-terminal Cys on another. Highly efficient for 30-50 AA segments. Used for proteins and very long peptides.

What To Expect

Long peptide projects take 6-10 weeks. Purity targets may need adjustment — >90% is often realistic where >98% isn't achievable. And the cost per amino acid increases significantly above 50 residues.