Unparalleled Solid Phase Peptide Peptide Synthesis

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UnparalleledPeptide SynthesisChemistry TechnologiesPeptide SynthesizersPeptide CleavageSPPS ReagentsWe Simplify Science

ContentsCEM Overview2 Innovations in Microwave Peptide Synthesis2 Founding Fathers3 Corporate LegacyChemistry TechnologiesHE-SPPS4 6 CarboMAXTM8 One Pot Coupling/DeprotectionPeptide Synthesizers1011121213131416Sequential vs ParallelSynthesizer ComparisonDiscover BioTMLiberty LiteTMLiberty BlueTMLiberty Blue HT12TMLiberty PRIMETMAccessories & UpgradesPeptide Cleavage17 Razor SPPS Reagents18 Fmoc Amino Acids19 Oxyma Pure19 Resins (ProTide , Polystyrene)Large Scale Microwave Peptide Synthesis22 Liberty PRO Customers24 Testimonials25 Supportcempeptides.com

CEM OverviewInnovationsin MicrowavePeptide Synthesis1978 CEM Corporation founded as anew company, based on microwavelaboratory instrumentation2001 CEM launches a single mode microwavesystem for chemical synthesis2003 CEM develops the world’s first automatedmicrowave peptide synthesizer12007 CEM publishes research for optimized methodsfor aspartimide formation and epimerizationunder microwave SPPS22013 Liberty Blue peptide synthesizer developedbased on High Efficiency Solid Phase PeptideSynthesis (HE-SPPS)2014 HE-SPPS methodology published32016 CEM launches new universal load resinseliminating the need for pre-loaded resinshistorically used2016 CEM offers the world’s first large-scale microwavepeptide synthesis, with capabilities of up to 500grams of a purified peptide, in a single batch2016 CEM develops improved carbodiimide couplingmethods for peptide synthesis at elevatedtemperature (CarboMAX )2017 CEM develops a novel one-pot coupling/deprotection process reducing SPPS cycletime and waste usage (Liberty PRIME )Founding Fathers (circa 1980)Chemist: Dr. Michael J. Collins (Middle)Electrical Engineer: Ron Goetchius (Left)Mechanical Engineer: Bill Cruse Jr. (Right) ollins J.M., Collins M.J., Steorts R.C. Biopolymers 71, 361 2003C Palasek S., Cox Z., Collins J. J. Pept. Sci. 13, 143-148 20073 Collins, J., Porter K., Singh S., Vanier G. Org. Lett. 16, 940-943 2014 122

Corporate LegacyFounded in 1978 by our current CEO, Dr. Michael J. Collins,CEM has pioneered the field of microwave chemistry.For nearly 40 years we have designed and developedlaboratory instrumentation and scientific methods (bothmicrowave-based and non-microwave technologies) that areused by major companies, prestigious research institutes,and universities around the world. The company’s majorproducts provide unique solutions for compositionalanalysis of food and chemical samples, acid digestion forelemental analysis, and chemical synthesis of peptidesand small molecules.CEM is a private company with global headquarters outsideCharlotte, North Carolina, along with offices in England,Germany, Japan, France, Italy, Singapore, and Ireland. Thecompany’s annual revenue is 90M USD (2017) with morethan 300 employees worldwide. Since 2003, CEM haspioneered the area of microwave peptide synthesis. Thecompany sells an elite line of microwave-based peptidesynthesizers, based on unique high efficiency solid phasepeptide synthesis (HE-SPPS) which provides unmatchedpurity, ultra-fast cycle times, and up to a 90% reduction intotal waste, compared to traditional technologies. Morethan 600 peptide synthesizers from CEM have beeninstalled throughout the world.3

HE-SPPSHigh EfficiencySolid Phase PeptideSynthesis (HE-SPPS)HE-SPPS is a significant advancement for solid phasepeptide synthesis. It originates from our pioneeringwork in developing microwave assisted SPPS,introduced at the 2003 American Peptide Symposium.1At this time, we introduced a new process for makingpeptides, based on the use of microwave energy forboth the deprotection and coupling steps in SPPS.This technology has demonstrated improvements forthousands of peptides with CEM’s peptide synthesisinstrumentation.2 To support microwave SPPS, wehave also utilized in-situ fiber optic temperaturemonitoring to provide true internal solution temperaturecontrol. This is essential for fast reaction heatingwith temperature control, as it is well known that theoutside of a reaction vessel can be at a significantlydifferent temperature than the inside.3In 2013, we developed an improved methodologyfor microwave SPPS, based on the use of highertemperature carbodiimide based coupling at 90 C, alongwith the elimination of all washing after each couplingstep.4 These insights led to significant time and solventsavings, while providing peptides of incredibly high purity.The more acidic coupling environment with carbodiimidechemistry overcomes coupling issues for cysteine(epimerization) and arginine (γ-lactam formation), whichwere previously an issue under more basic couplingconditions (ex. HCTU/DIEA). The instrumentation designused on CEM’s Liberty BlueTM peptide synthesizer is alsoa critical component of HE-SPPS to eliminate inefficientinternal fluidic and reagent path cleaning that increaseswaste generated. HE-SPPS used on the Liberty Blue isnow used in hundreds of laboratories worldwide andprovides very fast, high purity peptides with incrediblylow waste generated.Collins, J.M., Collins, M.J., and Steorts, R.C., "A Novel Method for SolidPhase Peptide Synthesis Using Microwave Energy" Biopolymers, 71,361 2003.2US7393920; US7582728; US8058393; JP47736953M. Herrero, J. Kremsner and C.O. Kappe, "Nonthermal MicrowaveEffects Revisited: On the Importance of Internal TemperatureMonitoring and Agitation in Microwave Chemistry," J. Org. Chem., vol.73, pp. 36 – 47, 2008.4J. Collins, K. Porter, S. Singh and G. Vanier, “High-Efficiency Solid PhasePeptide Synthesis (HE-SPPS),” Org. Lett., vol. 16, pp. 940-943, 2014.14

Selected Peptides Synthesized with HE-SPPSPeptideSequenceUPLC PuritySynthesis TimeTotal Waste (mL)65-74VQAAIDYING93%44 m154 mLJR-10merWFTTLISTIM-NH267%49 m170 mLABRF 1992GVRGDKGNPGWPGAPY82%1 h 37 m272 mLABC-20merVYWTSPFMKLIHEQCNRADG-NH273%2h7m340 mLThymosinSDAAVDTSSEITTKDLKEKKEVVEEAEN-NH261%2 h 11 m468 H272%3 h 49 m1019 mLACPb-amyloidSynthesize Standard andComplex Peptide Branched PeptidesCyclized PeptidesDisulfide BondingGlycopeptidesHigh Throughput SynthesisN-Methyl PeptidesPeptide ThioestersPeptoidsPhospho-peptidesPNA5

CarboMAXTM (Enhanced Carbodiimide Chemistry)Faster Coupling: Improved Puritywith Less EpimerizationCoupling with carbodiimide chemistry hassignificant benefits over aminium/phosphoniumsalts (ex. HATU, HCTU, PyBOP) at elevatedtemperature. This includes major reductions ofepimerization for cysteine and γ-lactam formationof arginine. However, activation by carbodiimides isrelatively slow. We developed an improved couplingprocess which allows for faster formation of thekey O-acylisourea intermediate by increasing theamount of carbodiimide to 2 equivalents relative tothe amino acid.1Reduced Epimerization (ex. Liraglutide)By forming more activated amino acid faster thanstandard carbodiimide chemistry the subsequentcoupling will happen quicker. This provides not onlya faster coupling time, but also less epimerizationfrom less time as a sensitive activated amino acid.This methodology termed CarboMAX is patentpending and exclusively licensed for use on CEM’speptide synthesizers.UPLC-MS Analysis of crude Liraglutide (CarboMAX)6EpimerDIC/Oxyma (%)CarboMAX 0.3D-HisN/AN/AD-Ile 0.10 0.10L-allo Ile 0.10 0.10D-allo Ile 0.10 0.10D-Leu0.170.13D-Lys 0.100.1D-Phe0.20.16D-Ser0.160.12D-Thr 0.10 0.10 0.10 0.10D-Trp0.24 0.10D-Tyr0.120.11D-Val 0.10 0.101Patent Pending: US15686719; EP17188963.7

Improved PurityPeptideSequence% Crude PurityDIC/Oxyma% Crude ainin 1GIGKFLHSAGKFGKAFVGEIMKS7179Dynorphin AAK(g-Glu-palmitoyl) EFIAWLVRGRG74881-34Stabilizing Acid-sensitive LinkagesMulti-phosphorylated peptide idesMany important side chain modifications are sensitiveto acidic activators, such as Oxyma Pure and HOBtused under elevated temperature. With traditionalcarbodiimide chemistry, this can lead to undesirablecleavage of sensitive groups, such as phospho andO-linked carbohydrates.CarboMAX Synthesis(Fmoc-AA/DIC/Oxyma Pure/DIEA) – 1/1/1/0.4We developed a patented process of incorporationof 1 equivalent base to stabilize these linkageswhile using carbodiimide chemistry at elevatedtemperature. This method which is part of CarboMAXchemistry is only available on CEM’s peptidesynthesizers and allows access to synthesis ofthese peptides at high temperatures withunmatched speed and purity.3Patent Pending: US20160176918; EP3037430;JP2016138090; CN105713066; AU2017204172Standard Synthesis(Fmoc-AA/DIC/Oxyma Pure) – 1/1/17

One-Pot Coupling/DeprotectionUnparalleled Speed and EfficiencyTraditional solid phase peptide synthesis involves the useof iterative and separate deprotection and coupling stepswith washing in-between. This is based on the assumptionthat undesirable amino acid insertions can occur withoutcomplete draining and washing between each step. In2013, it was demonstrated that washing after the couplingstep can be eliminated without effect on peptide purity.1The Liberty PRIMETM takes this further by using a new onepot coupling and deprotection process.2 This techniqueinvolves addition of the deprotection reagent (base) directlyto the undrained post-coupling mixture. The ability to dothis is based on the insight that faster reaction kineticsin the solution phase promote rapid hydrolysis or selfcondensation of the active ester, thereby avoiding potentialside reactions at the resin bound amino functionality. TheFmoc removal then proceeds uninterrupted at elevatedtemperature. An optimized use of reagents results inan essentially neutral reaction mixture towards the endof deprotection step. This new procedure offers severaladvantages such as (a) approximately 90% reduction insolvent requirement for the deprotection step, (b) 75%reduction in solvent requirement for post-deprotectionwashings, (c) faster deprotection step since the microwaveramp time is not needed, and (d) shorter cycle time due toabsence of the post-coupling drain eWashDeprotection2 min. 10 sec.Utilization of the one-pot coupling/deprotectionmethodology requires the ability to consistently addprecise small volumes of concentrated base. To achievethis, the Liberty PRIME incorporates a new dedicatedpumping module with the ability to rapidly add thedeprotection reagent precisely at the end of the couplingstep in volumes as low as 0.25 mL. The pre-calibratedpump module does not require on-going calibration therebyavoiding drifting delivery amounts. Additionally, the mainsolvent and the activator (Oxyma Pure) are also deliveredthrough similar individual pumps within the module forimproved performance.J. Collins, K. Porter, S. Singh and G. Vanier, “High-EfficiencySolid Phase Peptide Synthesis (HE-SPPS),” Org. Lett., vol. 16,pp. 940-943, 2014.2Patent Pending: US20170226152; WO20170705121Integrated pumping module utilized on the Liberty PRIME8

Peptide Synthesis on the Liberty PRIME3SequenceCrude Purity(UPLC-MS)Total Synthesis TimeTotal Chemical Waste65-74VQAAIDYING-NH294%25 m92 mLABC-20 merVYWTSPFMKLIHEQCNRADG-NH283%48 m172 mLJR-10 merWFTTLISTIM-NH270%25 m92 -NH257%1 h 36 m273 mL7-37HAEGTFTSDVSSYLEGQAAKEFIAWLVKGRG47%1 h 14 m217 mLPnIA(A10L)GCCSLPPCALNNPDYC-NH277%43 m112 mLCirculin AGIPCGESCVWIPCISAALGCSCKNKVCYRN79%1 h 10 m252 %1 h 14 m264 mLPeptideACPGLP1ABC-20 mer3JR-10 merExenatideGLP17-37Refer to CEM Application Note, "Liberty PRIME – Ultrafast Peptide Synthesis at Elevated Temperature"Minimal EpimerizationThe potential for epimerization was then investigatedon the elevated temperature coupling methods usedon the Liberty PRIME. In particular, cysteine andhistidine are known to be sensitive to epimerizationduring coupling. The epimerization level wastherefore investigated through a well-knownstandard method involving hydrolysis, subsequentderivatization, and gas chromatography analysis(C.A.T. GmbH). Epimerization levels observed withHBTU/DIEA activation at room temperature werefound to be higher than those from 90 C standardor CarboMAX couplings, as well as from 105 CCarboMAX coupling on the Liberty PRIME. Useof Fmoc-His(Boc)-OH instead of Fmoc-His(Trt)-OHallowed coupling temperatures of 90 C or 105 Cwithout any increase in epimerization levels. Theseresults further demonstrate that standard HE-SPPSor CarboMAX coupling methods are particularly wellsuited for peptide synthesis at elevated temperature.Epimerization Levels of Cysteine andHistidine in ABC 20merConventionalLiberty BlueLiberty PRIMERT - HBTU/DIEA90 C CarboMAX105 C 0.68%EpimerFmoc-His(Trt)-OH; bFmoc-His(Boc)-OH; cFmoc-Cys(Trt)-OHa9

Sequential vs ParallelUnparalleled AdvantagesSequential PeptideSynthesis Advantages Single peptides synthesized fast Faster Purification Workflow (purify as you go) Precise control at each step Higher purity peptides Simple to use & maintain instrumentationResin Loader AdvantagesOptional modular resin loading options are available,which allows up to 24 peptides to be synthesizedsequentially. The resin loader comes in a 12-positionmodule with an additional 12-position module that canbe coupled to it.With rapid cycle times, and the ability to synthesize12 – 24 peptides unattended, the Liberty Blue HT12TMand the Liberty PRIMETM provide exceptional throughputcompared to conventional parallel systems, but withconsiderably better purity.10

Synthesizer ComparisonPick the Synthesizer That's Best for YouLiberty LiteCycle TimeLiberty Blue HT12Liberty PRIMELiberty PRO4 minutes4 minutes2 minutes15 – 45 minutes (3 L – 15 L)Waste/Cycle 40 mL (0.1 mmol)16 mL (0.1 mmol)16 mL (0.1 mmol)8.5 mL (0.1 mmol)VariableScale Range0.005 – 5 mmol0.005 – 5 mmol0.005 – 5 mmol0.005 – 4 mmol15 – 1000 mmol(3 L, 8 L, 15 L)PeptidePositions1112241Amino AcidPositions2027272715OtherPositions4444 (upgrade to 5 available)4Flex-AddTM:Amino Acids &ActivatorsFlex-Add:Amino Acids &ActivatorsFlex-Add:Amino Acids &ActivatorsFlex-Add:Amino AcidsPositive DisplacementPump, Full Bottle Add:Amino AcidsTimed Delivery:Wash & DeprotectionTimed Delivery:Wash & DeprotectionTimed Delivery:Wash & DeprotectionPre-Calibrated Pumps:Wash, Deprotection &Oxyma PurePositive DisplacementPump, 0.05 – 10 L: Wash,Deprotection & Activators(2 positions)Dimensions 20" W x 18" D x 30" H 51 cm x 46 cm x 76 cm 20" W x 18" D x 30" H 51 cm x 46 cm x 76 cm 27" W x 18" D x 30" H 69 cm x 46 cm x 76 cm 42" W x 18" D x 30" H 107 cm x 46 cm x 76 cm 65” W x 40” D x 70” H 165 cm x 102 cm x 178 cmUpgradesUpgrade to theLiberty Blue HT12 HT24 HT24GMP DocumentationGMP DocumentationAccessoriesRazor Cleavage System Integrated Camera, Razor Cleavage System Flex-Add Large Scale Integrated Camera Razor Cleavage System Flex-Add Large Scale Integrated Camera Razor Cleavage System Vessel head holder 1L bottle cradlesFluidDelivery15 minutesLiberty Blue11

Discover BioTMManual Microwave Peptide SynthesizerLiberty LiteMicrowave Peptide SynthesizerOverviewOverviewThe world's best selling microwave peptidesynthesizer is also available in a researchscale manual system that offers a costeffective alternative to purchasing peptides.Enhance your laboratory's capabilitieswith the benefits of microwave-assistedpeptide synthesis.An entry-level option for the globallyrecognized Liberty Blue technology. TheLiberty Lite provides advantages overexisting peptide synthesizers.FeaturesFeatures Integrated module for washing and addingdeprotection Flex-Add critical reagent delivery system(patented) Easy access port for addition of activatedamino acids True Internal fiber-optic temperature control True Internal fiber-optic temperature control 0.005 - 5 mmol scale range 0.005 - 1 mmol scale range Ability to upgrade to Liberty Blue 20 amino acid positions Ability to upgrade to Liberty Blue12TMChemistry TechnologyChemistry Technology CarboMAX CarboMAX

Liberty BlueTMMicrowave Peptide SynthesizerLiberty Blue HT12TMHigh-ThroughputMicrowave Peptide SynthesizerOverviewOverviewThe Liberty Blue Automated MicrowavePeptide Synthesizer is the gold standard forpeptide synthesis. It features unmatched4-minute cycle times along with a 90%solvent reduction based on High EfficiencySolid Phase Peptide synthesis (HE-SPPS),developed in 2013.The Liberty Blue HT12 features all theadvantages of the Liberty Blue with theadded capability of the HT12 resin loader.This allows for the automated sequentialsynthesis of up to 12 different peptides.FeaturesFeatures Flex-Add critical reagent delivery system(patented) Flex-Add critical reagent delivery system(patented) True Internal fiber-optic temperature control True Internal fiber-optic temperature control 27 amino acid positions 27 amino acid positions 0.005 - 5 mmol scale range 0.005 - 5 mmol scale range Integrated Camera (optional) Integrated Camera (optional) Ability to upgrade to Liberty Blue HT12Chemistry TechnologyChemistry Technology HE-SPPS CarboMAX HE-SPPS CarboMAX13

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Liberty PRIME High-Throughput Microwave Peptide SynthesizerOverviewThe Liberty PRIME peptide synthesizer is the mostadvanced platform available for microwave peptidesynthesis. It features a revolutionary one-potdeprotection and coupling process, allowing for aremarkable 2-minute cycle time, with only 8.5 mLwaste per cycle (at 0.1 mmol). Individual 20-mers every 45 minutesPerformanceScaleCycle TimeAA Equiv.Waste/Cycle0.1 mmol2 m 10 s58.5 mL0.3 mmol3 m 40 s520 mL0.4 mmol3 m 50 s420 mL B atches of 24 peptides (20-mers) every 20 hours,with only 4.5 liters total waste producedEnhanced HardwareChemistry Technology One-Pot Coupling/Deprotection CarboMAXThe Liberty PRIME features enhanced delivery optionsof the main solvent and Deprotection solutionscompared to the Liberty Blue system. These reagentsare delivered by a pre-calibrated pumping system,not requiring calibration or affected by restrictionchanges in the delivery path. This reduces systemmaintenance and provides an ideal system for GMPenvironments that is free of calibration.15

Accessories & UpgradesMake Your Synthesizer Even Better68%JR 10mer:WFTTLISTIM-NH2Scale:1.0 mmolCycle Time:10 minFlex-Add (Large Scale)Designed for routine syntheses at larger scales( 0.5 mmol), this upgrade allows for optimizeddeliveries of larger volumes. At these scales, timesavings 40% are achieved.Integrated CameraThe newly introduced camera for theLiberty Blue system enables researchersto monitor microwave peptide synthesis asnever before. This fully integrated accessoryprovides complete visibility of the reaction vesselat any time with 5 mega-pixel quality (2560 x1920) and 720p video (1280 x 720) capability.This option is beneficial for optimization ofsynthetic methods and system troubleshooting.Pressure Rated BottlesPressure rated, stainless steel bottles incorporatingvisual liquid level detection. Available in 2 L, 5 L,10 L, and 20 L sizes (GL45 cap size).16

Razor Rapid Peptide Cleavage SystemOverviewCleave up to 12 peptides in only 30 minutes.The Razor features a compact design that easilyfits in a fume hood and allows for temperature at /- 1 C control for up to 12 different vessels.Cleavage is typically complete in 30 minutes forstandard peptides and allows for draining into acentrifuge tube for subsequent centrifugation.This system is ideal for both single peptides andlarge batches.Peptide: Fmoc-YGRKKRRQRRRConditions: TFA/TIS/H2O/DODT (92.5/2.5/2.5/2.5)7% ð30 minutes, room temperature E levated Temperature Cleavage BlockWith /- 1 C Control V alve Control For Independently DrainingEach Vessel93% ð C onvenient Tray For Holding & TransportingEach Collection Tube C ompact Design That Easily Fits In StandardFume Hoods30 minutes, Razor17

SPPS ChemicalsHigh Quality ChemicalsAvailable OnlineCEM offers a complete suite of peptide synthesis reagents foroptimized SPPS, whether using conventional synthesis or microwaveirradiation. This includes a complete library of standard and unique,high-quality Fmoc amino acids, PEG and polystyrene resins, andthe powerful Oxyma Pure activator. Using CEM’s unique high-qualityreagents provides the highest purity peptides, with CEM’s innovativemethodology and instrumentation.Fmoc Amino AcidsExtremely High Quality at an Affordable Price18OverviewStandard SpecificationsUsing Fmoc amino acids of lower quality can havea significant impact on peptide purity and yield,resulting in hard to separate impurities and eventotal synthesis failures. CEM’s Fmoc amino acidsare the highest quality available on the market andprovide the best purities and yields possible forpeptide synthesis. HPLC purity 99.0%Enantiomeric purity 99.8%100% fully synthetic amino acids Continuously used and tested in CEM’s peptidesynthesis laboratoryPre-weighedFull LibraryEliminate yourweighing step byusing amino acidsthat have beenpre-weighedspecifically for yourLiberty system.A catalogue ofFmoc aminoacids is availablefor synthesizingstandard andmodified peptides,for use with anypeptide synthesizer.

Oxyma PureThe Perfect Activator for Elevated TemperatureOverviewOxyma Pure used with DIC produces peptides with increased yield and decreased epimerization, when used asan alternative to HOBt.1 This safe, non-explosive auxiliary nucleophile works with carbodiimide coupling strategiesto provide the best results for a peptide synthesis. Additionally, the use of DIC/Oxyma avoids side reactionsassociated with high levels of base ( 1 equiv. DIEA), using onium salt methods such as HBTU/DIEA.1R. Subirós-Funosas, et al. (2009) Chem. Eur. J., 15, 9394.ResinsHigh Quality Unique Resins for SPPSOverviewA full library of PEG and polystyrene resins for SPPS. CEM’s SPPS resins are of the highest quality and optimizedfor the synthesis of standard and difficult peptides, with a variety of linkers.ClOHNnPS Core PEG ed on aPEG-PS corewith optimalswelling, ProTide isrecommended forsynthesis of very longand difficult peptides.High quality, preloaded, polystyreneresins are great forsynthesis of standardand difficult peptides.PS (1% DVB)19

ProTideTM ResinsOptimized PEG Resin Core withCl-TCP(Cl) and Cl-MPA Universal LinkersProTide resins contain an ideal PEG and polystyrene core, leading to an optimized environment for the synthesis ofdifficult peptides, with excellent swelling properties. New Cl-TCP(Cl) and Cl-MPA linkers incorporated onto ProTide,eliminate the necessity for purchasing resins with pre-loaded C-terminal amino acids. The C-terminal amino acidreacts with the linker-chloride, in the presence of potassium iodide (KI)1, N,N-diisopropylethylamine (DIEA), andmicrowave irradiation. The process is automatically carried out on CEM's microwave peptide synthesizers, usingpre-programmed methods in the software. The result, any amino acid can be loaded on the resins in 10 minutes.Key Advantages: A utomated, high-temperature loading procedurecomplete in 10 min, whereas room temperaturetakes up to 24 hours A voids coupling reagents; therefore, eliminatingepimerization and dipeptide formation that canoccur during loading N o longer need to buy/store 20 different,pre-loaded acid-linked resins20 E xhibit strong stability towards hydrolysis duringstorage and handling T CP(Cl) is hyperacid sensitive and will produceprotected peptides with 1% TFA/DCM and furtherminimizes diketopiperazine and 3-(1-piperidinyl)alanine formation212 Sandhya K., Ravindranath B. Tetrahedron Lett. 49, 2435 2008Heinlein C., Silva D., Tröster A., Schmidt J., Gross A., Unverzagt C.Angew. Chem. 50, 6406 2011

Rink Amide ProTide Resin (LL)The ultimate resin recommended for longer and more difficult sequencesof peptide amides. Based on ideal swelling properties from a TentaGel core, incorporating PEG PS with a loading of 0.15 – 0.25 mmol/g. Thisresin is unmatched for the routine synthesis of difficult peptides, even 75 amino acids.Rink Amide ProTide ResinA powerful resin recommended for the synthesis of peptides with amidelinkages 30 amino acids. Based on ideal swelling properties fromincorporating a PEG PS core with a loading of 0.55 - 0.8 mmol/g.Cl-TCP(Cl) ProTide ResinA powerful resin recommended for the synthesis of peptides with acidlinkages 30 amino acids. Based on ideal swelling properties from aTentaGel core, incorporating PEG PS with a loading of 0.4 – 0.6 mmol/g.This resin features an activated chloride linker, allowing for attachmentof the first amino acid in an unactivated form. This resin is recommendedfor protection of C-terminal cysteine and proline residues, due to itssteric protection against diketopiperazine formation and 3-(1-Piperidinyl)alanine formation.Cl-MPA ProTide Resin (LL)The ultimate resin recommended for longer and more difficult sequencesof peptide acids. Based on ideal swelling properties from a TentaGel core, incorporating PEG PS with a loading of 0.15 – 0.25 mmol/g. Thisresin is unmatched for the routine synthesis of difficult peptides even, 75 amino acids. This resin features an activated chloride linker,allowing for attachment of the first amino acid in an unactivated form.21

Liberty PRO Automated Production Scale Microwave Peptide SynthesizerIntroducing Liberty PROAvailable OptionsThe world’s first large-scale microwave peptidesynthesizer. Allows for the batch synthesisof peptides up to 500 grams with rapiddelivery times. Instrumentation (Liberty PRO) Low cost & rapid delivery times I mproved synthesis efficiency withmicrowave irradiation B atch sizes up to 500 grams of purifiedpeptide (15 L reaction vessel) M atch synthesis profiles of peptides madeon the Liberty Blue22 L arge-scale custom peptide synthesis servicesContact Us To Get Started 800-726-3331 peptide.support@cem.com

Synthesis ExamplesPeptide Sequence: 9 merResin: Rink Amide AM PS (0.75 mmol/g)Excess Reagents: 2.0 foldLiberty BlueTMLiberty PROTMScale: 0.1 mmolScale: 700 mmolSynthesis Time: 9 hPeptide Sequence: 7 merResin: Rink Amide AM PS (0.97 mmol/g)Excess Reagents: 2.5 foldLiberty BlueLiberty PROScale: 0.1 mmolScale: 360 mmolSynthesis Time: 6 h23

“ The Liberty Blue is fast, reliable, and makesdifficult peptides in high purity. We arevery satisfied with the Liberty Blue andwould highly recommend it for both proteinsynthesis and methodological development.”Prof. Fernando AlbericioGroup Leader Chemistry & Molecular PharmacologyInstitute for Research in Biomedicine (IRB)University of Barcelona“ The Liberty Blue system is unquestionablythe best peptide synthesizer availabletoday and represents the major workhorsefor PeptiDream (12 systems). It is highlyrecommended to any company looking tosynthesize peptides chemically, specificallythose containing nonstandard amino acids.” Dr. Patrick C. ReidPresident and DirectorPeptiDream Inc.“ We are very satisfied with the Liberty Bluesystem. The system is one of the best peptidesynthesizers available today for research andmedicinal chemists.HE-SPPS using LibertyBlue, features overwhelming speed.”Dr. Hajime HibinoResearch ChemistPeptide Institute“ The Liberty Blue is the best peptidesynthesizer on the market. It’s synthesisspeed and purity are unmatched. Using theLiberty Blue has also made our subsequentpurifications easier, which is a major benefit.”Prof. Anna Maria PapiniCoordinator of Interdepartmental LaboratoryPeptLab

Worldwide Support for Peptide SynthesisWe are where you are.Many companies say theyhave great customer service,at CEM, we prove it.KnowledgeableSales PeopleExperiencedField TechniciansExpertChemistsWith an average of15 years with CEM.Close by, to keep youup and running.To help with custom oradvanced applications.

cem.comOver 50,000systems soldworldwideUnited em.comCEM has been anISO-certified facilitysince 1994France33 (01) 69 35 57 80info.fr@cem.comAll systems serviced &supported by expertswith an average of 15years of experienceCEM invests 12% ofannual revenue intoR&D, the result.11 R&D 100 awardsGermany, Austria,Switzerland(49) 2842-9644-0info@cem.deItalyJapanUnited Kingdom( 39)035896224info.srl@cem.com 81-3-5793-8542info@cemjapan.co.jp(44) 1280-822873info.uk@cem.comIQ/OQ/PQValidation bycertified CEMTechniciansIreland 353 (0) 1 885 1752info.ireland@cem.comFor distributors in other regions, visit cem.com/contact 2019 CEM Corporation. All Rights Reserved. Worldwide patents issued and pending. Liberty Blue ,Liberty Lite , Liberty PRIME , Liberty Pro , Razor , CarboMAX , Flex-Add , & ProTide aretrademarks of CEM Corporation. TentaGel is a trademark of Rapp Polymere GmbH.B129v612/19

Solid Phase Peptide Synthesis (HE-SPPS) HE-SPPS is a significant advancement for solid phase peptide synthesis. It originates from our pioneering work in developing microwave assisted SPPS, introduced at the 2003 American Peptide Symposium.1 At this time, we introduced a new process for making peptides, based on the use of microwave energy for