SPPS RESIN FOR HIGH PURITY PEPTIDE SYNTHESIS - Zalety
IDEAL ENVIRONMENT FOR PEPTIDE SYNTHESIS
The formation of secondary structures, either through intra- or inter-molecular aggregation, is a known problem in SPPS that is often encouraged by a hydrophobic resin environment1, such as a traditional polystyrene (PS) resin cross-linked with divinylbenzene (DVB). In contrast, SpheriTide® resin provides a more hydrophilic environment that contains amide bonds just like the growing peptide backbone, which discourages the peptide from aggregating with itself (intra-molecular aggregation). SpheriTide resin allows for higher purities and yields compared to non-polar resins where intra-molecular aggregation may limit the efficiency of the deprotection and/or coupling reaction.
BETTER PERFORMANCE AT HIGHER LOADING
The unique properties of the SpheriTide® resin allow for high purity syntheses of difficult peptides at extremely high loadings. Several peptides were prepared under identical synthesis conditions2 using a 1.04 mmol/g Rink Amide SpheriTide® (HL) resin and a 0.59 mmol/g Rink Amide MBHA polystyrene resin. As demonstrated by Glucagon 1-29 peptide3, the 1-27 fragment belonging to Z Domain of Protein A4, and PnIA(A10L) Conotoxin5 below, in each case, the SpheriTide (HL) resin outperformed the polystyrene resin.
IMPROVED SYNTHESIS PURITY WITH HL SPHERITIDE RESIN†
|0.59 mmol/g Rink amide MBHA
||0.75 mmol/g Rink amide MBHA
||1.04 mmol/g Rink amide SpheriTide
|Influenza Virus Hemagglutinin
|PnIA (A10L) Conotoxin
|1-27 Z Domain of Protein A
|† Standard HE-SPPS cycles (2,2,3 mL DMF washes) + 2 x 2min at 90 °C coupling for Arg. Glucagon used a 10 min 50 °C His coupling method. All samples lyophilized.
Glucagon 1-29 Peptide = HSQGTFTSDYSKYLDSRRAQDFVQWLMNT-NH2
GREATER REPRODUCIBILITY & HIGHER QUALITY PEPTIDES
Clustering of linker sites within a resin bead results in crowding and can lead to lower synthesis efficiency. Traditional polystyrene-based resins are prepared by heat-induced radical polymerization leading to random variations in cross-linking and functionalizing sites. In contrast, SpheriTide resins are highly structured. Cross-linking only occurs at the amine sites which are spaced with a minimum distance between sites, improving both peptide quality and batch-to-batch reproducibility between resin samples.
CONTROLLED SWELLING IN TFA
SpheriTide resins display controlled swelling in TFA. This can be an issue when using PEG-based resins which require large TFA/resin ratios for fully covering the resin.
SpheriTide® is a registered trademark of Spheritech Ltd., is patented under PCT/EP2012/057264 and exclusively licensed by CEM Corporation..
 Fmoc Solid Phase Peptide Synthesis – A Practical Approach, W.C. Chan and P.D. White, Eds. 2000, Oxford University Press: New York. p. 30, 118.  All syntheses were performed using HE-SPPS methodology on the Liberty Blue peptide synthesizer (J.M. Collins, K.A. Porter, S.K. Singh, G.S. Vanier Org. Lett. 2014, 16, 940-943.)  J.S. Pedersen, D. Dikov, D.E. Otzen, Biochemistry 2006, 45, 14503-15512.  Simon et al. ChemBioChem 2014, 15, 713 - 720.  Abdel-Aal, A. M.; Papageorgiou, G; Quibell, M.; Offer, J. Chem Commun. 2014, 50, 8316 –8319.