Vibrational circular dichroism of polypeptides, V. A study of 3<sub>10</sub>‐helical‐octapeptides

Yasui, Sritana C.; Keiderling, Timothy A.; Bonora, Gian Maria; Toniolo, Claudio

doi:10.1002/bip.360250107

Cited by 80 publications

(67 citation statements)

References 27 publications

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“…This result is in good agreement with the published NMR data on the L-Val2 analog 4 39 of the same, fully 3 10 -helical, parent peptide 3, 38 and beautifully parallels that of an NMR study on an Ala-rich peptide, where an ␣-helical sequence was identified in the middle and short 3 10 -helical stretches at both termini. 61 A previous detailed structural investigation on an N ␣ -acylated octapeptide ester (equivalent to a heptapeptide alkylamide as far as its capability of intramolecular H-bond formation is concerned), characterized by seven Aib residues and a single C ␣ -trisubstituted ␣-amino acid (L-Leu6) near the C-terminus (2), unequivocally established the onset of a fully developed, rigid, regular 3 10 -helical conformation, [30][31][32][33][34][35] as observed in the -(Aib) 8 -homopeptide sequence (1). 36,37 Taken together, these findings support the view that, even in the case of a very high percentage of C ␣ -tetrasubstituted ␣-amino acids discussed here, the precise positioning of the single C ␣ -trisubstituted residue in the sequence may have a dramatic effect on the helical structure of the peptide backbone.…”

Section: Discussionmentioning

confidence: 98%

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: Discussionmentioning

confidence: 98%

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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“…2,33,34,40,52,55 Again, these patterns are somewhat sensitive to the degree of C Ralkylation and have small frequency shifts in different solvents. The intensity ratio between the amide I couplet and amide II negative VCD is an important characteristic for distinguishing 3 10 -and R-helices when coupled with their detailed band shapes as secondary evidence.…”

Section: A4a5omentioning

confidence: 95%

Experimental and Theoretical Spectroscopic Study of 3₁₀-Helical Peptides Using Isotopic Labeling to Evaluate Vibrational Coupling

et al. 2011

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Coupling between the amide linkages in a peptide or protein is the key physical property that gives vibrational spectra and circular dichroism sensitivity to secondary structures. By use of (13)C isotopic labeling on individual and pairs of amide C═O groups, the amide I band for selected residues was effectively isolated in designed hexa- and octapeptides having dominant 3(10)-helical conformations. The resultant frequency and intensity responses were measured with IR absorption, vibrational circular dichroism (VCD), and Raman spectroscopies and simulated with density functional theory (DFT) based computations. Band fitting the spectral components and correlating the results to the computed coupling between selected labeled positions were used to determine coupling constant signs and to estimate their magnitudes for specific sequences. The observed frequency and intensity patterns, and their variation between IR and VCD with label position in the sequence, follow the theoretical predictions to a large degree, but are complicated by end effects that alter the local force field (FF) for some residues in these short peptides. These FF variations were overestimated in the theoretical models which may be evidence of structural variations not included in the model. By analyzing the simulations with different coupling models, the coupling constants were determined to lie in a range (positive) +3-5 cm(-1) for sequential residues (i,i+1) and with (negative) -3 cm(-1) as an upper bound for alternate ones (i,i+2). The sequential amide coupling for 3(10)-helices is weaker than for α-helices but has the same sign and is larger than and oppositely signed as compared to 3(1)-, or poly-(Pro)(n) type-II, helices.

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“…Having values so close to the prediction error for total helix, the 310 component, though a significant structural feature, proves to have too little impact on the spectral correlation to fractional structure. It is important to realize that 310-helices d o give qualitatively identifiable VCD spectra in oligopeptides (Yasui et al, 1986a), but for the amide I' they are very weak and discrimination is dependent on amide 11 measurement. The ECD spectra of 3,,-helices are poorly distinguished from those of a-helices (Toniolo et al, 1991).…”

Section: Limitations Of the Methodsmentioning

confidence: 99%

Comparison of and limits of accuracy for statistical analyses of vibrational and electronic circular dichroism spectra in terms of correlations to and predictions of protein secondary structure

et al. 1995

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This work provides a systematic comparison of vibrational CD (VCD) and electronic CD (ECD) methods for spectral prediction of secondary structure. The VCD and ECD data are simplified to a small set of spectral parameters using the principal component method of factor analysis (PC/FA). Regression fits of these parameters are made to the X-ray-determined fractional components (FC) of secondary structure. Predictive capability is determined by computing structures for proteins sequentially left out of the regression. All possible combinations of PC/FA spectral parameters (coefficients) were used to form a full set of restricted multiple regressions with the FC values, both independently for each spectral data set as well as for the two VCD sets and all the data grouped together. The complete search over all possible combinations of spectral parameters for different types of spectral data is a new feature of this study, and the focus on prediction is the strength of this approach. The PC/FA method was found to be stable in detail to expansion of the training set. Coupling amide I1 to amide I' parameters reduced the standard deviations of the VCD regression relationships, and combining VCD and ECD data led to the best fits. Prediction results had a minimum error when dependent on relatively few spectral coefficients. Such a limited dependence on spectral variation is the key finding of this work, which has ramifications for previous studies as well as suggests future directions for spectral analysis of structure. The best ECD prediction for helix and sheet uses only one parameter, the coefficient of the first subspectrum. With VCD, the best predictions sample coefficients of both the amide I' and I1 bands, but error is optimized using only a few coefficients. In this respect, ECD is more accurate than VCD for a-helix, and the combined VCD (amide I'+II) predicts the P-sheet component better than does ECD. Combining VCD and ECD data sets yields exceptionally good predictions by utilizing the strengths of each. However, the residual error, its distribution, and, most importantly, the lack of dependence of the method on many of the significant components derived from the spectra leads to the conclusion that the heterogeneity of protein structure is a fundamental limitation to the use of such spectral analysis methods. The underutilization of these data for prediction of secondary structure suggests spectral data could predict a more detailed descriptor.

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Vibrational circular dichroism of polypeptides, V. A study of 3₁₀‐helical‐octapeptides

Cited by 80 publications

References 27 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

Experimental and Theoretical Spectroscopic Study of 3₁₀-Helical Peptides Using Isotopic Labeling to Evaluate Vibrational Coupling

Comparison of and limits of accuracy for statistical analyses of vibrational and electronic circular dichroism spectra in terms of correlations to and predictions of protein secondary structure

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Vibrational circular dichroism of polypeptides, V. A study of 310‐helical‐octapeptides

Cited by 80 publications

References 27 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

Experimental and Theoretical Spectroscopic Study of 310-Helical Peptides Using Isotopic Labeling to Evaluate Vibrational Coupling

Comparison of and limits of accuracy for statistical analyses of vibrational and electronic circular dichroism spectra in terms of correlations to and predictions of protein secondary structure

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Vibrational circular dichroism of polypeptides, V. A study of 3₁₀‐helical‐octapeptides

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

Experimental and Theoretical Spectroscopic Study of 3₁₀-Helical Peptides Using Isotopic Labeling to Evaluate Vibrational Coupling