Comparison of various coupling reagents in solid-phase aza-peptide synthesis

Arujõe, Meeli; Ploom, Anu; Mastitski, Anton; Järv, Jaak

doi:10.1016/j.tetlet.2017.07.063

Cited by 11 publications

(9 citation statements)

References 21 publications

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“…Attempting to further improve coupling efficiency, we explored the use of PyOxim, a relatively new Oxyma-based phosphonium salt coupling reagent that has shown high efficiency in SPPS of hindered and cyclic peptides. − However, no improvements were seen over DIC/Oxyma, with polymers still only achieving low molecular weights ( P4_PyOxim_microwave , M w,GPC(PEO calibrated) = 3.2 kg/molor M w,GPC(PS calibrated) = 18.2 kg/mol).…”

Section: Results and Discussionmentioning

confidence: 99%

Rapid Synthesis of Silk-Like Polymers Facilitated by Microwave Irradiation and Click Chemistry

et al. 2020

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Silk is a natural fiber that surpasses most man-made polymers in its combination of strength and toughness. Silk fibroin, the primary protein component of silk, can be synthetically mimicked by a linear copolymer with alternating rigid and soft segments. Strategies for chemical synthesis of such silk-like polymers have persistently resulted in poor sequence control, long reaction times, and low molecular weights. Here, we present a two-stage approach for rapidly synthesizing silk-like polymers with precisely defined rigid blocks. This approach utilizes solid-phase peptide synthesis to create uniform oligoalanine "prepolymers", followed by microwave-assisted step-growth polymerization with bifunctional poly(ethylene glycol). Multiple coupling chemistries and reaction conditions were explored, with microwave-assisted click chemistry yielding polymers with M w ∼ 14 kg/mol in less than 20 min. These polymers formed antiparallel β-sheets and nanofibers, which is consistent with the structure of natural silk fibroin. Thus, our strategy demonstrates a promising modular approach for synthesizing silk-like polymers. Article pubs.acs.org/Biomac

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Section: Results and Discussionmentioning

confidence: 99%

Rapid Synthesis of Silk-Like Polymers Facilitated by Microwave Irradiation and Click Chemistry

et al. 2020

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“…Recent successes using benzotriazol-1-yloxytris(pyrrolidinophosphonium-hexafluorophosphate (PyBOP)/ N , N -diisopropylethylamine (DIEA) [25] and (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholino-carbenium hexafluorophosphate (COMU)/DIEA [26,27] in difficult couplings to aza-amino acids led us to try these activating agents; however, 9 was obtained in low conversions in both cases (6–13%, Table 1, entries 2 and 3). We next investigated N,N,N′,N′ -tetramethylchloroformamidinium hexafluorophosphate (TCFH)/ N -methylimidazole (NMI) (Table 1, entry 4), which was recently developed [28] to couple sterically hindered carboxylic acids with non-nucleophilic aniline derivatives and sterically hindered amino acids, including valine.…”

Section: Resultsmentioning

confidence: 99%

Aza-Amino Acids Disrupt β-Sheet Secondary Structures

et al. 2019

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Cα to N substitution in aza-amino acids imposes local conformational constraints, changes in hydrogen bonding properties, and leads to adaptive chirality at the nitrogen atom. These properties can be exploited in mimicry and stabilization of peptide secondary structures and self-assembly. Here, the effect of a single aza-amino acid incorporation located in the upper β-strand at a hydrogen-bonded (HB) site of a β-hairpin model peptide (H-Arg-Tyr-Val-Glu-Val-d-Pro-Gly-Orn-Lys-Ile-Leu-Gln-NH2) is reported. Specifically, analogs in which valine3 was substituted for aza-valine3 or aza-glycine3 were synthesized, and their β-hairpin stabilities were examined using Nuclear Magnetic Resonance (NMR) spectroscopy. The azapeptide analogs were found to destabilize β-hairpin formation compared to the parent peptide. The aza-valine3 residue was more disruptive of β-hairpin geometry than its aza-glycine3 counterpart.

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“…Like other phosphonium-based reagents, PyOxim proved efficient for cyclization using H-Ala-Ala-NMeAla-Ala-Ala-OH as a model peptide. 95 Bis(2-oxo-3-oxazolidinyl)phosphorodiamidic chloride (BOP-Cl, Figure 13), 102 which is not related to the phosphonium salt BOP, is the most important member of the organophosphinic family of coupling reagents, which have shown broad applications, mainly for the solution synthesis of N-Me-containing peptides. 103,104 The modest acceptance of BOP-Cl in the solid-phase mode is probably a result of its poor performance.…”

Section: Stand-alone Oxymapure-based Coupling Reagentsmentioning

confidence: 99%

“…COMU also finds applications in the preparation of Weinreb amide in solution and even for the esterification of tertiary alcohols . In the solid-phase mode, this reagent has proved optimal for the preparation of both peptoids and aza-peptides …”

Section: Comumentioning

confidence: 99%

“…93 In the solid-phase mode, this reagent has proved optimal for the preparation of both peptoids 94 and aza-peptides. 95 Recently, Withey and Bajic from MacEwan University (Edmonton, Alberta) proposed a second-year undergraduate laboratory experiment in which the students prepared the insect repellent, N,N-diethyl-3-methylbenzamide (DEET), from 3-methylbenzoic acid and N,N-diethylamine using COMU as coupling reagent. 96 According to this report, the advantage of this experiment from an educational perspective is that the reaction can be monitored visually by virtue of the color change associated with the conversion, and all byproducts are conveniently water-soluble.…”

Section: ■ Introductionmentioning

confidence: 99%

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Choosing the Right Coupling Reagent for Peptides: A Twenty-Five-Year Journey

Alberício

El‐Faham

2018

Org. Process Res. Dev.

130

109

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This work is not a typical review that is trying to cover all coupling reagents in-depth. This is a personal accountit is written in the first personseeking to summarize the 25 years of collaboration that has brought the release of several products onto the market, together with strategies for the efficient synthesis of peptides and also other molecules of biological interest, broadly adopted by the scientific community.

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Comparison of various coupling reagents in solid-phase aza-peptide synthesis

Cited by 11 publications

References 21 publications

Rapid Synthesis of Silk-Like Polymers Facilitated by Microwave Irradiation and Click Chemistry

Rapid Synthesis of Silk-Like Polymers Facilitated by Microwave Irradiation and Click Chemistry

Aza-Amino Acids Disrupt β-Sheet Secondary Structures

Choosing the Right Coupling Reagent for Peptides: A Twenty-Five-Year Journey

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