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Peptide Labs Health
Peptide LabsHealth

Solid-Phase Peptide Synthesis (SPPS)

Our advanced Fmoc-based solid-phase synthesis platform enables the rapid, high-fidelity production of peptides up to 100 residues in length.

Process Steps

1

Resin Loading

The C-terminal amino acid is anchored to a functionalized polymeric resin support via a cleavable linker. We use Rink amide and Wang resins optimized for Fmoc chemistry, with typical loading capacities of 0.3-0.8 mmol/g.

2

Fmoc Deprotection

The Fmoc protecting group on the alpha-amino group is removed using 20% piperidine in DMF, exposing the free amine for the next coupling step. Deprotection is monitored by UV absorbance at 301 nm.

3

Amino Acid Coupling

The next Fmoc-protected amino acid is activated with a coupling reagent (HATU/HBTU with DIPEA) and reacted with the free amine on the resin-bound peptide. Coupling efficiency exceeds 99.5% per cycle under optimized conditions.

4

Repeat Cycles

Deprotection and coupling steps are repeated iteratively from C-terminus to N-terminus until the full target sequence is assembled on the resin. Our automated synthesizers complete each cycle in 15-45 minutes.

5

Cleavage and Deprotection

The completed peptide is cleaved from the resin and all side-chain protecting groups are simultaneously removed using a TFA-based cleavage cocktail (typically 95% TFA with scavengers). The crude peptide is precipitated in cold diethyl ether.

6

Purification

The crude peptide is purified by preparative reversed-phase HPLC to achieve the desired purity grade. Fractions are analyzed by analytical HPLC and mass spectrometry before pooling and lyophilization.

Overview

Solid-Phase Peptide Synthesis (SPPS) is the cornerstone of modern peptide manufacturing. Invented by Robert Bruce Merrifield in 1963, the technique involves the stepwise assembly of a peptide chain on an insoluble polymeric support (resin), enabling the use of excess reagents and simple washing steps to drive reactions to completion. At Peptide Labs Health, we employ state-of-the-art Fmoc-based SPPS with automated synthesizers capable of producing peptides ranging from simple dipeptides to complex sequences exceeding 100 amino acid residues.

Our synthesis platform incorporates microwave-assisted coupling for difficult sequences, pseudoproline dipeptide building blocks to disrupt on-resin aggregation, and real-time monitoring of coupling efficiency via colorimetric and spectrophotometric methods. These technologies, combined with rigorous process optimization and quality control, enable us to routinely achieve crude purities of 70-85% for standard sequences and greater than 60% for complex or long peptides, minimizing the purification burden and maximizing overall yield.

Capabilities

Our SPPS platform supports a comprehensive range of modifications, including N-terminal acetylation, C-terminal amidation, disulfide bridge formation, lactam cyclization, PEGylation, fluorescent labeling (FITC, TAMRA, Cy5), biotinylation, and phosphorylation. We maintain an inventory of over 300 Fmoc-protected amino acid building blocks, including non-natural amino acids, D-amino acids, and specialty residues, enabling the synthesis of virtually any peptide sequence with custom modifications to meet your research needs.