Enzymatic resolution of α,α-disubstituted α-amino acid esters and amides

Kaptein, Bernard; Boesten, W. H. J.; Broxterman, Quirinus B.; Peters, P. J. H.; Schoemaker, Hans E.; Kamphuis, J.

doi:10.1016/s0957-4166(00)80217-7

Cited by 90 publications

(41 citation statements)

References 20 publications

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“…40,41 It involves a combination of organic synthesis for the preparation of the racemic ␣-amino acids followed by the use of a broadly specific aminopeptidase to achieve optical resolution. The Z N ␣ -protected, C ␣ -methylated ␣-amino acids [42][43][44] were acti-…”

Section: Synthesis and Characterization Of Peptidesmentioning

confidence: 99%

Factors governing 3₁₀‐helix vs α‐helix formation in peptides: Percentage of C^α‐tetrasubstituted α‐amino acid residues and sequence dependence

et al. 2002

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As an additional step toward the dissection of the factors responsible for the onset of 3(10)-helix vs alpha-helix in peptides, in this paper we describe the results of a three-dimensional (3D) structural analysis by x-ray diffraction of the N(alpha)-acylated heptapeptide alkylamide mBrBz-L-Iva-L-(alphaMe)Val-L-Abu-L-(alphaMe)Val-L-(alphaMe)Phe-L-(alphaMe)Val-L-Iva-NHMe characterized by a single (L-Abu3) C(alpha)-trisubstituted and six C(alpha)-tetrasubstituted alpha-amino acids. We find that in the crystal state this peptide is folded in a mixed helical structure with short elements of 3(10)-helix at either terminus and a central region of alpha-helix. This finding, taken together with the published NMR and x-ray diffraction data on the all C(alpha)-methylated parent sequence and its L-Val2 analog (also the latter heptapeptide has a single C(alpha)-trisubstituted alpha-amino acid) strongly supports the view that one C(alpha)-trisubstituted alpha-amino acid inserted near the N-terminus of an N(alpha)-acylated heptapeptide alkylamide sequence may be enough to switch a regular 3(10)-helix into an essentially alpha-helical conformation. As a corollary of this work, the x-ray diffraction structure of the N(alpha)-protected, C-terminal tetrapeptide alkylamide Z-L-(alphaMe)Val-L-(alphaMe)Phe-L-(alphaMe)Val-L-Iva-NHMe, also reported here, is clearly indicative of the preference of this fully C(alpha)-methylated, short peptide for the 3(10)-helix. As the same terminally blocked sequence is mixed 3(10)/alpha-helical in the L-Abu3 heptapeptide amide but regular 3(10)-helical in the tetrapeptide amide and in the parent heptapeptide amide, these results point to an evident plasticity even of a fully C(alpha)-methylated short peptide.

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Section: Synthesis and Characterization Of Peptidesmentioning

confidence: 99%

Factors governing 3₁₀‐helix vs α‐helix formation in peptides: Percentage of C^α‐tetrasubstituted α‐amino acid residues and sequence dependence

et al. 2002

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“…-Peptide Synthesis and Characterization. For the large-scale production of the enantiomerically pure l-(aMe)Nva, we exploited an economically attractive and generally applicable chemo-enzymatic synthesis developed by DSM Pharmaceutical Products a few years ago [19].…”

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confidence: 99%

Conformational Effects on the Electron‐Transfer Efficiency in Peptide Foldamers Based on α,α‐Disubstituted Glycyl Residues

Gatto

Porchetta

Stella

et al. 2008

Chemistry & Biodiversity

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Peptide foldamers based on alpha,alpha-disubstituted glycyl residues were synthesized and chemically characterized to investigate the effects of the electric field generated by a 3(10)-helix on the rate of intramolecular photoinduced electron-transfer reactions. To this end, two new octapeptides having identical sequences were suitably side-chain functionalized with the same electron-transfer donor-acceptor pair, but inverting the position of the pair along the main chain. The electron-transfer rate constants, measured by time-resolved spectroscopy techniques (nanosecond transient absorption and time-resolved fluorescence), indicated that, in the case of the 3(10)-helix, the electrostatic effect is significant, but smaller than that obtained for alpha-helical peptides. This finding can be likely ascribed to the distortion of the H-bond network with respect to the helical axis taking place in the former secondary structure. Overall, these results could have implications on electron-transfer phenomena in model and biomembranes facilitated by peptaibiotics.

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“…11 (S)-2-Amino-2-methylundecanoic acid successfully replaces the N-terminal n-octanoyl chain essential for activity in the membraneactive lipopeptaibol antibiotic trichogin GA IV, 12 and studies concerning the conformational preferences of model peptides containing this amino acid have shown that (R)-2-amino-2-methylundecanoic acid favors the formation of a left-handed 3 10 -helical conformation. 13 Both enantiomers of this amino acid have been obtained by enzymatic resolution of a-amino amides 14 using Mycobacterium neoaurum ATCC25795, a broadly specific amino acid amidase.…”

Section: Resultsmentioning

confidence: 99%

Allylation and propargylation of chiral cyanopropanoates: An efficient route to long chain α‐substituted α‐methyl α‐amino acids

et al. 2003

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Enzymatic resolution of α,α-disubstituted α-amino acid esters and amides

Cited by 90 publications

References 20 publications

Factors governing 3₁₀‐helix vs α‐helix formation in peptides: Percentage of C^α‐tetrasubstituted α‐amino acid residues and sequence dependence

Factors governing 3₁₀‐helix vs α‐helix formation in peptides: Percentage of C^α‐tetrasubstituted α‐amino acid residues and sequence dependence

Conformational Effects on the Electron‐Transfer Efficiency in Peptide Foldamers Based on α,α‐Disubstituted Glycyl Residues

Allylation and propargylation of chiral cyanopropanoates: An efficient route to long chain α‐substituted α‐methyl α‐amino acids

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Enzymatic resolution of α,α-disubstituted α-amino acid esters and amides

Cited by 90 publications

References 20 publications

Factors governing 310‐helix vs α‐helix formation in peptides: Percentage of Cα‐tetrasubstituted α‐amino acid residues and sequence dependence

Factors governing 310‐helix vs α‐helix formation in peptides: Percentage of Cα‐tetrasubstituted α‐amino acid residues and sequence dependence

Conformational Effects on the Electron‐Transfer Efficiency in Peptide Foldamers Based on α,α‐Disubstituted Glycyl Residues

Allylation and propargylation of chiral cyanopropanoates: An efficient route to long chain α‐substituted α‐methyl α‐amino acids

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Factors governing 3₁₀‐helix vs α‐helix formation in peptides: Percentage of C^α‐tetrasubstituted α‐amino acid residues and sequence dependence

Factors governing 3₁₀‐helix vs α‐helix formation in peptides: Percentage of C^α‐tetrasubstituted α‐amino acid residues and sequence dependence