Ultra-Efficient Solid Phase Peptide Synthesis (UE-SPPS)

Exceptional Purity

Headspace Gas Flushing¹

Simply put, a cleaner reaction environment facilitates cleaner synthesis outcome.

CEM's patented Headspace Gas Flushing technology removes volatile deprotection base from the reaction headspace before condensation can occur on upper vessel surfaces. Base condensation and (often inopportune) reaction solution reentry can heavily impact synthesis purity, especially in longer sequences where even small impurity products can quickly accumulate.

Complete evacuation of the deprotection base from both the reaction solution and headspace has an additional advantage: elimination of extensive and repetitive vessel washing steps. Continue reading for more information on efficiency benefits.


JR 10-mer

CarboMAX Coupling²

When synthesis purity matters, so does your coupling strategy.

Carbodiimide-promoted coupling methodologies offer a host of advantages over onium salt-promoted coupling (e.g. HBTU/DIEA) approaches, especially at elevated temperature. Benefits of carbodiimide methodology include both drastically lower enolization/ epimerization rates and elimination of other base-catalyzed side reaction occurrences.


R = Amino Acid Side Chain
Y = Side Chain Protecting Group
A = OH, NH

CarboMAX™ is a further enhancement to standard carbodiimide methodology for peptide coupling. Developed at CEM, CarboMAX routinely enables higher coupling efficiency and lower epimerization rates than even standard carbodiimide methodologies. Learn more here.

		Crude Purity
Peptide	Sequence	Standard	CarboMAX
Thymosin	SDAAVDTSSEITTKDLKEKKEVVEEAEN	63%	75%
GRP	GRPVPLPAGGGTVLTKMYPRGNHWAVGHLM	62%	74%
Bivalirudin	fPRPGGGGNGDFEEIPEEYL	80%	82%
1-34PTH	SVSEIQLMHNLGKHLNSMERVEWLRKKLQDVHNF	67%	85%
35-55MOG	MEVGWYRSPFSRVVHLYRNGK	77%	91%
Magainin 1	GIGKFLHSAGKFGKAFVGEIMKS	71%	79%
Dynorphin A	YGGFLRRIRPKLKWDNQ	74%	82%
Liraglutide*	HAEGTFTSDVSSYLEGQAAK(γ-Glu-palmitoyl)EFIAWLVRGRG-OH	74%	88%

^*Synthesized with ~ 0.32 mmol/g Fmoc-Gly-Wang PS resin

Microwave Energy³

Better reaction conversion, every step of the way.

Microwave irradiation is a well-established technology for enhancing the purity of peptides made via solid phase peptide synthesis and has been described in hundreds of publications worldwide. A global pioneer in microwave SPPS, CEM introduced the world's first automated microwave peptide synthesizer in 2003.

Unmatched Efficiency

Incredible Waste Reduction

Reduce waste production, not synthetic yield/purity.

By employing carbodiimide-promoted coupling methodology, the UE-SPPS process eliminates post-coupling wash step requirements. Any residual activated amino acid from coupling is quenched by the subsequently added deprotection base before any side reactions can occur.

Expanding upon this principle, UE-SPPS utilizes a “one-pot” coupling and deprotection step where a small amount of deprotection solution is added to the existing coupling solution, reducing the combined solvent needs for the two reactions by almost 50%. (I.e. The solvent from the coupling step is reused in the following deprotection step.)
Through development of the Headspace Gas Flushing technology (the evaporative-based process described above), UE-SPPS also eliminates post-deprotection wash step requirements. The volatile deprotection base (pyrrolidine) is rapidly evaporated from the vessel at temperatures > 90 °C simultaneous to a rapid microwave assisted deblocking step. Flushing of the headspace gas prevents volatilized deprotection base from condensing on the upper surfaces of the reaction vessel. Together, these processes render the peptidyl resin ready for the next coupling reaction, sans washing.

Through a remarkable combination of methodology optimization, reagent selection, and engineering advancements, UE-SPPS reduces waste production by up to 95%, and all without sacrificing synthesis yield and purity.

	Traditional SPPS	UE-SPPS
Waste per AA addition*	100 mL	< 5 mL
Waste per 10-mer*	1 L	< 50 mL

*@ 0.1mmol