Influence of steric effects in solid-phase aza-peptide synthesis

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

doi:10.1016/j.tetlet.2018.04.021

Cited by 9 publications

(2 citation statements)

References 21 publications

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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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Section: Resultsmentioning

confidence: 99%

Aza-Amino Acids Disrupt β-Sheet Secondary Structures

et al. 2019

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“…Additionally, we have demonstrated that the rate of aza-peptide bond formation in compound XII sig nificantly depends on the bulkiness of the aza-amino acid side chain R and of the amino acid side group R 1 [74,75]. The influence of these substituents was quantified with the graph shape index values Ξ, which were specifically derived for characterization of the amino acid side chain bulkiness [76].…”

Section: Aza-peptide Bond Synthesismentioning

confidence: 99%

Aza-peptides: expectations and reality

Arujõe¹,

Järv²,

Mastitski³

et al. 2022

PEAS

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The replacement of the α-carbon atom in an α-amino acid structure by a nitrogen atom yields alkylcarbazic acids, also known as α-aza amino acids. Although the topology of α-amino acids and α-aza amino acids is similar, their chemical and stereochemical properties are significantly different. For this reason, the application of the common solid-phase peptide synthesis (SPPS) protocol cannot be used for aza-peptide bond synthesis without changes. On the other hand, the aza-peptide bond is more stable than the common peptide bond, therefore these compounds are very attractive targets for drug design. In this review, we summarize data on aza-peptide bond chemistry, with implications for the improvement of aza-peptide chemical synthesis.

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Solid phase submonomer azapeptide synthesis

Bowles

Proulx

2021

Synthetic and Enzymatic Modifications of the Peptide Backbone

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Influence of steric effects in solid-phase aza-peptide synthesis

Cited by 9 publications

References 21 publications

Aza-Amino Acids Disrupt β-Sheet Secondary Structures

Aza-Amino Acids Disrupt β-Sheet Secondary Structures

Aza-peptides: expectations and reality

Solid phase submonomer azapeptide synthesis

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