Trifluoroacetic acid

Nα-Fmoc-protected amino acids, Rink amide resin, coupling reagents, N,N-diisopropylethylamine (DIEA), piperidine and trifluoroacetic acid (TFA) were purchased from Iris Biotech (Marktredwitz, Germany). Peptide synthesis solvents, reagents and CH₃CN for high-performance liquid chromatography (HPLC) were reagent grade, acquired from commercial sources and used without further purification unless otherwise noted.

Amino acids protected by 9-fluorenylmethyloxy carbonyl (Fmoc) where purchased from NovaBiochem, Watford, UK. Tenta Gel S NH₂ resin and Rink amide linker were purchased from Iris Biotech, Marktredwitz, Germany. Dimethylformamide (DMF), dichloromethane, diethyl ether, and methanol were of analytical grade (≥99.5%) and obtained from Fisher Scientific, Loughborough, UK. Triisopropylsilane (TIPS, ≥98.0% GC), phenol (≥99%), trifluoroacetic acid (TFA, ≥99%), and N,N-diisopropylethylamine (DIPEA, ≥99%) were obtained from Iris Biotech GmbH. 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU, ≥97%) was purchased from NovaBiochem, UK. Tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (DOTA-tri-t-Bu-ester) was purchased from Sigma Aldrich, Dorset, UK. All other reagents were of analytical grade.

5-Nitro-1H-indole-3-carboxaldehyde,
2-iodobenzonitrile, and silver(I) carbonate were purchased from abcr.
1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI·HCl)
and trifluoroacetic acid were purchased from IRIS biotech, while palladium
(10%) on activated charcoal, tert-butyl dicarbonate
(Boc₂O), palladium(II) acetate, 4-(dimethylamino)pyridine
(DMAP), sodium chlorite, and sulfamic acid were obtained from Sigma-Aldrich.
2-Formylpyridine, absolute dimethylformamide (DMF), tetra-n-butylammonium fluoride (TBAF), 4-toluenesulfonyl chloride, triethylamine,
sodium bicarbonate, magnesium sulfate, and borane solution (1 M in
THF) were bought from Fisher/Acros Organics. Triphenylphosphine, sodium
bicarbonate, and celite were purchased from Alfa Aesar. 2-Iodobenzeneethylamine
was prepared by using a literature protolol.^{28 (link)}Synthesis of the main organic scaffolds b₁–h₃ is described in detail in the Supporting Information. ¹H NMR spectra of intermediate species b₁, b₂, c₁–c₃, d₁–d₃, e₁–e₃, f₁–f₃, g₁–g₃, h₁, and h₂ are shown in Figures S36–S54.

N^α-Fmoc-protected amino acids, Fmoc-Rink Amide AM resin, 1-hydroxy-7-azabenzotriazole (HOAt), N-hydroxy-benzotriazole (HOBt), 2-(1H-benzotriazole-1-yl)- 1, 1, 3, 3-tetramethyluronium hexafluoro-phosphate (HBTU), N, N-diisopropylethyl-amine (DIPEA), piperidine, and trifluoroacetic acid were acquired from Iris Biotech (Marktredwitz, Germany). Biotage AB (Uppsala, Sweden) supplied the Rink Amide ChemMatrix resins. Unless otherwise stated, solvents and reagents for peptide synthesis, as well as CH₃CN for high-performance liquid chromatography (HPLC), were of reagent grade and purchased from commercial sources.

Coupling agents (HOAt, HBTU), Fmoc-Gly-Wang, Nα-Fmoc-protected amino acids, DIEA, piperidine, and trifluoroacetic acid were supplied by Iris Biotech (Marktredwitz, Germany). Remaining reagents and solvents were of analytical grade, commercially available, and were utilized without any further purification.

Chemical reagents and solvents for the peptide synthesis were of peptide-synthesis grade; solvents for HPLC were of HPLC grade. Fmoc-protected amino acids, Rink-amide MBHA resin (100–200 mesh, loading 0.57 mmol/g), N,N-diisopropylethylamine (DIPEA), piperidine, N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), dichloromethane (DCM), diethyl ether, and trifluoroacetic acid (TFA) were purchased from Iris Biotech (Germany). H-Asp(OtBu)-2-chlorotrityl resin (loading 0.60 mmol/g) was purchased from Merck Schuchardt OHG (Germany). Thioanisole (TIA), acetic anhydride, α-cyano-4-hydroxycinnamic acid, triisopropylsilane (TIS), 1,2-ethanedithiol (EDT), and acetonitrile (ACN) were purchased from Sigma Aldrich (Germany). 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and N-hydroxybenzotriazole (HOBt) were purchased from Biosolve (The Netherlands).