Spreadsheet: 1111635b-6c91-43e6-9017-3381c6e777c2
Sheet: Sheet1

Table 1S. Homo α-peptoid oligomer synthetic parameters | Unnamed: 1 | Unnamed: 2 | Unnamed: 3 | Unnamed: 4 | Unnamed: 5 | Unnamed: 6 | Unnamed: 7 | Unnamed: 8 | Unnamed: 9 | Unnamed: 10 | Unnamed: 11 | Unnamed: 12 | Unnamed: 13 | Unnamed: 14 | Unnamed: 15 | Unnamed: 16 | Unnamed: 17 | Unnamed: 18 | Unnamed: 19 | Unnamed: 20 | Unnamed: 21 | Unnamed: 22 | Unnamed: 23 | Unnamed: 24 | Unnamed: 25 | Unnamed: 26
Ref. # | [NAME] | Loading | Vendor | Reaction | Amine | Amt/coupling | Concn. | Solvent | T/oC | Time | μW | Acid | Concn. | Amt/coupling | Solvent | Coupling | Solvent | Concn | Amount | T/oC | Time | Yield | Purity | Oligo | Instrument | Comments
 | Type | mmol/g |  | scale /umol |  | mmol | mol/L |  |  | Mins | y/n |  | mol/L | mmol |  | Reagent |  | mol/L | mmol |  | Mins | % | % | length
TK
40 | TentaGel HL12902, 75um | 0.49 | Rapp Polymere | 750mg | benzyl
 |  |  |  |  | primary |  | 2 | DMF |  | 2x15s | y | ba | 2 |  | DMF | DIC | DMF | 3.2 |  |  | 2x15s |  |  | 9 | domestic microwave 1kW
42; 43; 44; 45 | TentaGel 140-170 um MB NH2 | 0.48-0.51 |  | 0.5 |  | 0.8 |  |  |  |  |  |  |  | 4.8 |  |  |  |  | 7.7 |  |  |  |  |  | domestic microwave 1kW | C-Met  is cleaved orthogonally with CNBr cyanogen bromide
22; 46 | Rink amide MBHA |  | Novabiochem
 | PS macrobeads 500um |  | Rapp Polymere | 1g, 500 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | domestic microwave 1kW
47; 46 | Knorr amide MBHA | 0.78 | Novabiochem |  |  |  | 2 | DMF |  | 2x15s | y | ba | 2 |  | DMF | DIC | DMF | 3.2 |  |  | 2x15s |  |  | 9 | domestic microwave 1kW | C-Cys to conjugate fluorescein
48, 19 | PS A-RAM macrobeads 500-560um | 0.55 | Rapp Polymere |  |  | 1.5-3 | 1 to 2 | DMF |  | 2x15s | y | ba | 2 | 2 | DMF | DIC | DMF | 3.2 | 3.2 |  | 2x15s |  |  | 4 | domestic microwave 1kW
49 | [NAME] 90um | 0.2-0.3 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 6 | domestic microwave 1kW
50, 51, 52 | TentaGel 140-170 um MB NH2 | 0.51 | Rapp Polymere | 2g, 1000 |  |  | 2 | DMF or DMSO | 37 | 60-90 | n | ba | 2.8 | 4.2 | DMF | DIC | DMF | 3.2 | 4.8 | 37 | 40-60 |  |  | 6, 8 | Rainin 12-channel peptide synthesizer | Added 2 C-terminal AA residues to facilitate trouble-free Edman sequencing
 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 25mL peptide synthesis vessel (Chemglass)
53, 54 | amine glass surface |  |  |  |  |  |  |  |  |  | n |  |  |  |  |  |  |  |  |  |  |  |  |  | digital photolithography | see text for description. >30000 features within a 1.5cm2 area of glass
55 | Rink amide MBHA | 0.73 | Novabiochem | 50mg, 37umol |  | 2 | 1 | DMF or DMSO | rt | 120 |  | ba | 2 | 2 | DMF | DIC | DMF | 2 | 2 | rt | 2x30 | 70-81 | 25-70 | 9 | Symphony automated peptide synthesizer
 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | (Protein Technologies Inc)
 |  |  |  |  |  |  |  |  | 37 | 60 |  | ba | 2 | 2 | DMF | DIC | DMF | 2 | 2 | 37 | 45 | 70-90 | 63-80 | 9 | NB Scientific Innova 4400 incubator shaker
KK
28, 33, 56, 37, 38 | Rink amide |  | Novabiochem | 60-70 | primary alkyl | 20eq | 1 | DMF | rt | 20 | n | ba | 1.2 | 20 eq | DMF | DIC | neat |  | 24 eq | rt | 20 |  | >98 | 7, 6 | tempo, hydroxyquinoline
57 | Rink amide | 0.69 | Novabiochem |  | aryl amine | 20 eq | 1.2 | DMF | rt | 960 |  |  |  |  |  | DIC | neat |  | 24 eq | rt | 90 |  |  | 6 | fritted syringe
 | 2-chlorotrityl resin | 1.3 | Novabiochem |  | aryl amine | 20 eq | 1.2 | DMF | rt | 960 |  |  |  |  |  | DIC | neat |  | 24 eq | rt | 90 |  |  | cyclo-6 | fritted syringe | pyBOP/DIEA in DMF with 2.4umol/mL soln, of linear peptide o/n at rt  for cyclization
34 | Rink amide | 0.69 |  | 70 |  |  |  |  |  | 960 |  |  |  |  |  |  |  |  |  |  | 90 |  | >85 | 7 | fritted syringe | [NAME] amine. Reductive debromination of N-bromoacetamide to N-acetamide
35 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 18
36 | Rink amide |  |  | 100mg | heterocyclic | 2 | 2 | DMF | 35 | 60 |  | ca | 0.4 | 0.34 | DMF | DIC | neat | 0.2 mL |  | rt | 20 |  | 56-95 | 5 |  | low yield for hydroxyquinoline submonomer amine due to steric effects. Ca  used after heterocyclic amine addition.
 |  |  |  |  |  | 1 | 1 | DMF | rt | 20 | n | ba | 0.4 | 0.34 | DMF | DIC | neat | 0.2 mL |  | rt | 20 |  |  | 5
58, 59 | Rink amide | 0.49 |  | 50 | phenylethyl | 1 | 1 | DMF | rt | 40 | n | ba | 1.2 | 1 | DMF | DIC | neat | 0.2 mL |  | rt | 20 |  |  | 13 | Illiad 2 robotic workstation, Charybdis Instruments
RNZ
60 | Rink amide | 0.6 | Novabiochem | 60 | primary | 1.2 | 1.2 | NMP | rt | 60 | n | ba | 1.2 | 1 | DMF | DIC |  |  |  | rt | 20 |  |  | 7 | Aapptec Apex 396 | N-benzylguanidine sidechain is lost under cleavage conditions
61 | Rink amide | 0.57 |  |  | histamine |  |  |  |  |  |  | ca |  |  |  |  |  |  |  |  |  |  |  | 36 | automated robot synthesizer | gives 2o amide at this position
62 | TentaGel -NH2 280-320um | 0.21
 | TentaGel Rink amine | 0.18 |  | 100mg, 18 |  | 1 | 1 | NMP | 35 | 20-120 | n | ba | 1.2 | 1 | DMF | DIC | neat |  | 1.2 | 35 | 20 | 39-69 | 50-95 | 5 | Automated peptide synthesizer | cleavable hydrophilic linker, halogen tag for tandem MS analysis
 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 18-24 | 58-72 | 10 | Automated peptide synthesizer
7, 8 | Rink amide | 0.57 | Novabiochem | 50 |  | 1.3-1.7 | 1.5-2.0 | NMP | 35 | 40-90 | n | ba | 1.2 | 1.35 | DMF | DIC | neat | 0.2 mL | 1.25 | 35 | 10 |  |  | 15 |  | Ligation. DIC:bromoacetic acid 0.93:1.0 optimal ratio
 | Sasrin resin |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | C-terminal aldehyde
 | 2-Chlorotrityl resin | 1.33 | Novabiochem |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | C-terminal thiol
63 | same as refs. 182, 195 |  |  |  |  |  | 1 | DMF | 35 | 20 |  |  |  |  |  |  |  |  |  |  |  | 55-95 | 85-95 | 5 |  | N-terminus conjugation
 | except amine solution
64 | Rink amide | 0.57 | Novabiochem | 50 | heterocyclic | 1.7 | 2 | NMP / DMF | 35, 45 | 60-180 | n | ba | 0.4 | 0.34 | DMF | DIC | DMF | 2 | 0.4 | 35, 45 | 5 | 45-93 | 10 to 87 | 15 | Automated peptide synthesizer | heterocyclic amines, anilines. Use of KI catalyst. Reduced haloacid concentration and reaction time
 |  |  |  |  |  |  |  |  |  |  | n | ca | 0.4 | 0.34 | DMF | DIC | DMF | 2 | 0.4 | 35, 45 | 5 | 71-92 | 78-95 | 15 | Automated peptide synthesizer
65 |  |  |  |  |  |  |  |  |  | 60, 90 | n | ba |  |  |  |  |  |  |  |  | 2x15 |  |  | 15 | Zymark robotic library synthesizer | a-chiral pendant group side chains
66 | Rink amide |  |  | 50 | lipid amine - see text |  |  |  |  |  | n | ba | 1.2 | 1 | DMF | DIC | neat | 0.2 mL |  | 35 | 45 |  |  | 36 |  | novel coupling for DMPE lipid amine - see text
67 | Rink amide | 0.47 | Novabiochem | 50 |  | 0.85 | 1 | [NAME] | 35 | 40 | n | ba | 1.2 | 1 | DMF | DIC | neat | 0.2 mL |  | 35 | 40 |  | 50-99 | 36
3, 68 | Rink amide |  | Novabiochem | 50, 100mg |  | 1 mL | 1 to 2 | [NAME] | rt | 120 | n | ba | 0.6 | 0.5 | DMF | DIC | DMF | 3.2 | 0.64 | rt | 30x2 | 70 | 50 | 5 |  | Methods Enzymol. Review
69 | Rink amide |  | Advanced |  |  |  |  |  |  |  | n | ba |  |  |  |  |  |  |  |  |  |  |  |  | Symphony multiple peptide synthesizer
 |  |  | Chemtech
2 | Rink amide | 0.45 |  | 50 |  | 2, 40 eq. | 0.25-2.5 | [NAME] | rt | 120 | n | ba | 0.7 | 0.6, 12 eq. | DMF | DIC | DMF | 3.9 | 0.6, 13 eq. | rt | 30x2 | 52-90 | 60-85 | 5
 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 86 | 65 | 25 |  | 0.6M HOBt inclusion dropped yield from 75% to 5%
AM / FA
70 | Rink amide AM RAM | 0.79 | Rapp Polymere | 80 |  | 50 eq. | 0.4 | DMF | 90 | 90s | y | ba | 0.4 | 30 eq. | DMF | DIC | DMF | 0.4 | 30 eq. | 35 | 30s |  |  | 5 | CEM Discover monomode microwave 50mL R.B. flask | 10 hrs. vs 4-5 days for 5-mers. Reagent concns. Lower than Blackwell uW procedure (194)
71 | Rink amide MBHA | 0.65 | Novabiochem | 160, 250 mg | amine with 1 eq. TEA | 0.64 |  | DMSO / DMF | rt | 240 | n | ca |  | 0.96 |  | DIC |  |  | 0.48 | rt | 60 |  | 60-80 | 3 | PP syringe with PE porous disk | [NAME] test for reaction completion
 | BAL MBHA | 0.7 | Novabiochem | 210, 300 mg | amine with 1 eq. TEA | 0.84 |  | DMSO / DMF | rt | 240 | n | ca |  | 1.26 |  | DIC |  |  | 0.63 | rt | 60 |  | 60-80 | 3 | PP syringe with PE porous disk | [NAME] test for reaction completion
72 | Rink amide |  |  |  | amine with 1 eq. TEA | 5 eq. |  | DMF | rt | 300x2 | n | ca |  | 20 eq. | DCM | DIC | DCM |  | 10 eq. | rt | 60x2 |  | 84-98 | 3 | PP syringe with PE porous disk | Kaiser or deClercq tests for acylation; Chloranil or [NAME] tests for amination.
 | BAL resin |  |  |  | amine with 1 eq. TEA | 5 eq. |  | DMF | rt | 300x2 | n | ca |  | 20 eq. | DCM | DIC | DCM |  | 10 eq. | rt | 60x2 |  | 84-98 | 3 | PP syringe with PE porous disk | Kaiser or deClercq tests for acylation; Chloranil or [NAME] tests for amination.
73 | Rink amide AM RAM | 0.7 |  | 280 | amine with 1 eq. TEA | 20 eq. |  | DM F | rt | 180 | n | ca |  | 20 eq. | 1:1  DMF:DCM | DIC |  |  |  | rt | 30 |  | 70 | 3 |  | Acylation & amination steps checked with chloranil test
74 | Rink amide AM RAM | 0.7 |  | 420 | amine with 1 eq. TEA | 5 eq., 2.1 | 5 mL | DMF | rt | 180 | n | ca |  | 5 eq., 2.1 | 1:2 DMF:DCM | DIC | 1:2 DMF:DCM | 5 mL | 5 eq. | rt | 30x2 |  | 0.8 | 3 | PP syringe with PE porous disk
75, 76 | Rink amide AM RAM | 0.7 |  | 490 | amine with 1 eq. TEA | 20 eq. |  | DMF | rt | 180x2 | n | ca chloride |  | 20 eq. | DCM | TEA | DCM |  | 20 eq. | 0 | 90x2 |  |  | 3
AB
23, 77 | Rink amide-MBHA LL (low loading) |  | Novabiochem |  | primary alkyl | 20 eq. |  | DMF | rt | 20 | n | ba | 1.2 | 20 eq. | DMF | DIC |  |  | 24 eq. | rt | 20 |  |  | 50 | C S Bio 036 autopeptide synthesizer | 50-mer
78 | Rink amide MBHA |  | Anaspec |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 20 | C S Bio 036 autopeptide synthesizer | 2,2,2-trifluoroethylamine
79 | Rink amide |  | Novabiochem | 250 |  |  | 1 | NMP | rt | 90-120 | n | ba | 1.2 |  | DMF |  |  |  |  | rt | 45 |  |  | 22
80, 81 | Rink amide |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 17 | ABI 433A automated peptide synthesizer
82 | 2-chlorotrityl resin |  | Novabiochem |  | Nspe | 10 eq. |  |  |  |  |  | 1,2-13C-ba | 0.6 |  | DMF |  |  |  |  |  |  |  |  | 9 |  | ca (2 eq.) used with KI catalyst for first submonomer addition
83 | Rink amide |  |  | 250 |  | 24 eq. | 1 | NMP or DCM | rt |  | n | ba | 1.2 | 200 eq. | DMF | DIC | neat | 1 mL | 44 eq. | rt | 60 | 38-76 |  | 12 to 17 | ABI 433A automated peptide synthesizer
84 | [NAME] resin |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 32-91 | 6 to 24 |  | C-substituted by reductive amination
HB
85 | Rink amide | 0.69 |  | 410 | nitroaromatic amine | 20 eq. | 0.8 | DMF | 95 | 90s | y | ba | 0.8 | 20 eq. | DMF | DIC | DMF | 0.8 | 20 eq. | 35 | 30 |  | 13-20 | 9 | Milestone MicroSYNTH multimodal microwave | Deactivated nitroaromatic amines require 60oC for 60 mins for bromide displacement, uW synthesizer
86 | Rink amide 100-200 mesh | 0.75 | Advanced | 75 mg, 56 | deactivated amines |  | 1 | DMF | 95 | 90s | y | ba | 2 |  | DMF | DIC | DMF | 2 |  | 35 | 30 |  | 56-93 | 5 | Milestone MicroSYNTH multimodal microwave
 |  |  | Chemtech |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 52-69 | 9 | Milestone MicroSYNTH multimodal microwave
DA
87 | Rink amide | 0.75 |  | 50 mg, 37 | Triazole monomer |  | 2 | DMF | 35 | 60 | n | ba | 0.4 | 0.25, 6.7 eq. | DMF | DIC | DMF | 2 | 0.3, 8 eq. | 35 | 20 |  |  | 8 |  | 1o amine.HCl with 1 eq. DIEA. 180 mins for first amination displacement.
88 | Rink amide TentaGel | 0.28 |  | 40 |  | 25 eq. | 1 - 1.5 | NMP or DMSO | rt | 150 | n | ba anhydride | 0.6 | 0.6, 15 eq. | NMP |  |  |  |  | rt | 40 | 10 to 30 |  | 10 | Pierce fritted PP tube | phosphoric and sulfonamide amine submonomers for water solubility
MB
89, 90, 91, 92 | Rink amide aminomethyl PS |  |  |  | Fmoc-N-R-Gly-OH | 3 eq. |  |  | 60 | 20 | y |  |  |  |  | DIC / HOBt | DMF | 0.1 | 3 eq. | 60 | 20 |  |  | 7 to 22 | Microwave assisted, 60oC coupling crucial to success
MD
93 | Rink amide | 0.45 | Anaspec | 23 mg, 10 | amine with 1eq. TEA | 0.2 mL | 0.8 | NMP | 40 | 90 | n | ca | 0.5 | 0.2 mL | DMF | DIC | DMF | 1 | 0.1 mL | rt | 15 | 2 to 38 | 90-98 | 4 | sonication for displacement reaction
94 | Rink amide | 0.45 |  | 23 mg, 10 |  |  | neat or 1 or 2 | neat or NMP | rt | 30 - 180 | n | ba | 1 | 0.2mL or 0.25mL | DMF | DIC | DMF | 1 | 0.2mL or 0.25mL | rt | 20 | 5.4-35 |  | 6, 11, 16 |  | glycosylated by click reaction
FdeR
95 | 2-chlorotrityl resin | 1.55 |  | 460 |  | 3 mL | 1 | DMF | rt | 30 | n | ba | 1.2 | 2.5mL | DCM | DIC | neat |  | 600 uL | rt | 20 |  | 68-80 | 6 |  | Glycosyl amines
96 | 2-chlorotrityl resin | 1.55 | Fluka |  | N-Fmoc, N-benzyl- |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | >90 | >95 | 10
 |  |  |  |  | oxyethylGly-OH
RMJL
97 | Rink amide TentaGel |  |  |  | Fmoc synthesis |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 8 to 12 |  | 10
98 | TentaGel S RAM | 0.24 |  | 250 | Fmoc-N-R-Gly-OH | 1 |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 26-37 |  | 11 | ABI 433A automated peptide synthesizer
[NAME]  29 | Rink amide AM |  |  |  | Fmoc-N-R-Gly-OH |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 12 |  | Sarcosine  and N-propagylglycine monomers for glycosylated peptoids
[NAME] 99 | Whatman 50 cellulose paper |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 7 | SPOT synthesis | bromophenol blue test
[NAME]100 | Rink amide MBHA |  |  | 100 | a-amino acids K, R, | 1.0, 10 eq. |  | DMF |  | 12 hr | n | ba | 1 | 2.0, 20 eq. | DMF | DIC | neat |  | 400 uL | rt | 120 |  |  | 11
 |  |  |  |  | Y, G with 1 eq. TEA
[NAME] 101 | Rink amide MBHA | 0.73 |  | 60 | Fmoc-N-R-Gly-OH |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  |  | 25-55 |  | 7 | Advanced Chemtech 348-omega peptide synthesizer
[NAME], 103 | Whatman 50 cellulose paper | 0.5-0.9 |  |  |  | 2 uL | 0.8 - 5 | NMP or water/ | rt | 15x3 | n | ba [NAME] | 1 | 2 uL | NMP |  |  |  |  | rt | 15x2 | 10 to 54 | 44-93 | 3, 6 | ABIMED AutoSpot Robot | SPOT synthesis
 |  | umol/cm2 |  |  |  |  |  | 0.05% Tween 20
K. Fukase 104 | TentaGel S RAM 130um | 0.25 | Rapp Polymere | 450 |  | 7 |  | [NAME] | rt | 180 or 240 | n | ba |  | 4.5 | DMF | DIC | DMF |  | 4.5 | rt | 90
M.C. Pirrung 105, 106 | Aminomethyl PS resin 500-550 um | 0.95 | Rapp Polymere | 2850 |  | 3.2 | 1 | [NAME] | rt | 720 | n | ba | 0.8 | 43 | DMF | DIC | neat |  | 43 | rt | 180
[NAME] 107 | MAMP resin |  |  |  | NaI catalyst |  |  | NMP | 80 | 960 | n | ca  chloride |  |  | THF | py |  |  |  | rt | 960 | 70 | 90 | 1 |  | Merrifield, [NAME]-methoxyphenyl resin. Addition of amine first
Burgess 108 | Rink amide MBHA | 0.72 |  | 100mg, 72 |  | 42 eq. | 2 | DMF or DMSO | 50 | 1 | y | ba | 2 | 42 eq. | DMF | DIC | DMF | 2 | 42 eq. | 50 | 1 |  | 99 | 3 | CEM Discover monomode microwave
Notes
TK=[NAME] group
KK=[NAME] group
RNZ=[NAME] group
AM / FA = [NAME] and Albericio groups
AB=Barron group
HB=[NAME] group
DA=[NAME] group
MB=Bradley group
MD=Disney group
FdeR=Riccadris group
RMJL=Liskamp group
ba=bromacetic acid
ca=chloroacetic acid