Turn and Helical Peptide Handedness Governed Exclusively by Side-Chain Chiral Centers

Royo, Soledad; Borggraeve, Wim M. De; Peggion, Cristina; Formaggio, Fernando; Crisma, Marco; Jiménez, Ana I.; Cativiela, Carlos; Toniolo, Claudio

doi:10.1021/ja043116u

Cited by 58 publications

(38 citation statements)

References 19 publications

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“…41,42 In addition, the analysis also allowed characterization of a novel side-chain to main-chain O i Á Á Á HÀ ÀN iþ1 -type interaction, in the latter sequence. 42 Encouraged from these results and the one reported by Toniolo and coworkers, 44 to explore further the influence of the preceding C -branched amphiphilic stereogenic center on the mainchain conformation, we describe here the crystal molecular structure of another correlated model peptide: Boc-Thr-Thr-NH 2 (1). The analysis provides unambiguous experimental evidence favoring the existence of a novel structural motif that topologically mimics a typical -turn, i.e., stabilized by a main-chain to main-chain C i ¼ ¼O Á Á Á HÀ ÀN iþ3 interaction, 29,[45][46][47][48][49][50] and the Asx-turns, i.e., stabilized by a side-chain to main-chain C i þ 1 ¼ ¼O Á Á Á HÀ ÀN iþ3 interaction.…”

Section: Introductionmentioning

confidence: 78%

“…Using two enantiomeric forms of nonproteinogenic 1-amino-c-2,t-3-diphenylcyclopropane-1-carboxylic acid, Toniolo and coworkers established the influence of C -side-chain chirality on the preferred main-chain conformation of homooligopeptides. 44 Taken together, what seems to emerge is that Thr-mediated short-range interactions possibly impart exclusive conformational restrictions, and subtle variation in the preferred rotameric distribution of the polar side chain can exert a dramatic influence on the main-chain conformation(s).…”

Section: Crystal Packingmentioning

confidence: 99%

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Characterization of β‐turn and Asx‐turns mimicry in a model peptide: Stabilization via CH · · · O interaction

Thakur

Kishore

2006

Biopolymers

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The chemical synthesis and single-crystal X-ray diffraction analysis of a model peptide, Boc-Thr-Thr-NH2 (1) comprised of proteinogenic residues bearing an amphiphilic Cbeta -stereogenic center, has been described. Interestingly, the analysis of its molecular structure revealed the existence of a distinct conformation that mimics a typical beta-turn and Asx-turns, i.e., the two Thr residues occupy the left- and right-corner positions. The main-chain torsion angles of the N- and C-terminal residues i.e., semiextended: phi = -68.9 degrees , psi = 128.6 degrees ; semifolded: phi = -138.1 degrees , psi = 2.5 degrees conformations, respectively, in conjunction with a gauche- disposition of the obligatory C-terminus Thr CgammaH3 group, characterize the occurrence of the newly described beta-turn- and Asx-turns-like topology. The preferred molecular structure is suggested to be stabilized by an effective nonconventional main-chain to side-chain Ci=O . . . H--Cgamma(i+2)-type intraturn hydrogen bond. Noteworthy, the observed topology of the resulting 10-membered hydrogen-bonded ring is essentially similar to the one perceived for a classical beta-turn and the Asx-turns, stabilized by a conventional intraturn hydrogen bond. Considering the signs as well as magnitudes of the backbone torsion angles and the orientation of the central peptide bond, the overall mimicked topology resembles the type II beta-turn or type II Asx-turns. An analysis of Xaa-Thr sequences in high-resolution X-ray elucidated protein structures revealed the novel topology prevalence in functional proteins (unpublished). In view of indubitable structural as well as functional importance of nonconventional interactions in bioorganic and biomacromolecules, we intend to highlight the participation of Thr CgammaH in the creation of a short-range C=O . . . H--Cgamma -type interaction in peptides and proteins.

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Section: Introductionmentioning

confidence: 78%

Section: Crystal Packingmentioning

confidence: 99%

Characterization of β‐turn and Asx‐turns mimicry in a model peptide: Stabilization via CH · · · O interaction

Thakur

Kishore

2006

Biopolymers

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“…It usually has a right‐handed ( P ) screw sense because of the asymmetric center of the α‐carbon of L‐α‐amino acids1. Several studies have attempted to control the helical screw sense of peptides2–10, and we have recently reported that a chiral cyclic α,α‐disubstituted α‐amino acid bearing only side‐chain chiral centers, (3 S ,4 S )‐1‐amino‐(3,4‐dimethoxy)cyclopentanecarboxylic acid [( S , S )‐Ac 5 c dOM ]11 controls the left‐handed ( M ) helical‐screw sense of its homopeptides12. Incidentally, α‐aminoisobutyric acid (Aib) is widely used as a strong helical inducer; however, it does not exhibit a helical‐screw sense bias because Aib is an achiral amino acid13–15.…”

Section: Introductionmentioning

confidence: 99%

Conformations of peptides containing a chiral cyclic α, α‐disubstituted α‐amino acid within the sequence of Aib residues

Demizu

Tanaka

Doi

et al. 2010

Journal of Peptide Science

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A single chiral cyclic α,α-disubstituted amino acid, (3S,4S)-1-amino-(3,4-dimethoxy)cyclopentanecarboxylic acid [(S,S)-Ac(5)c(dOM)], was placed at the N-terminal or C-terminal positions of achiral α-aminoisobutyric acid (Aib) peptide segments. The IR and (1)H NMR spectra indicated that the dominant conformations of two peptides Cbz-[(S,S)-Ac(5)c(dOM)]-(Aib)(4)-OEt (1) and Cbz-(Aib)(4)-[(S,S)-Ac(5)c(dOM)]-OMe (2) in solution were helical structures. X-ray crystallographic analysis of 1 and 2 revealed that a left-handed (M) 3(10)-helical structure was present in 1 and that a right-handed (P) 3(10)-helical structure was present in 2 in their crystalline states.

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“…Preliminary results of a part of this work have been reported. [29] Results and Discussion Synthesis and characterization: The preparation and characterization of the c 3 diPhe derivatives Boc-(R,R)-c 3 diPhe-OH [23] (Boc, tert-butyloxycarbonyl), Boc-(S,S)-c 3 diPhe-OH, [23] and Boc-(R,R)-c 3 diPhe-NHiPr [29] (iPr, isopropyl) were already reported. Peptide synthesis was performed step-by-step in solution beginning from the C-terminus.…”

Section: Introductionmentioning

confidence: 99%

Preferred 3D‐Structure of Peptides Rich in a Severely Conformationally Restricted Cyclopropane Analogue of Phenylalanine

Crisma

Borggraeve

Peggion

et al. 2005

Chemistry A European J

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Terminally blocked, homo-peptide amides of (R,R)-1-amino-2,3-diphenylcyclopropane-1-carboxylic acid (c3diPhe), a chiral member of the family of Calpha-tetrasubstituted alpha-amino acids, from the dimer to the tetramer, and diastereomeric co-oligopeptides of (R,R)- or (S,S)-c3diPhe with (S)-alanine residues to the trimer level were prepared in solution and fully characterized. The synthetic effort was extended to terminally protected co-oligopeptide esters to the hexamer, where c3diPhe residues are combined with achiral alpha-aminoisobutyric acid residues. The preferred conformations of the peptides were assessed in solution by FT-IR absorption, NMR, and CD techniques, and for seven oligomers in the crystal state (by X-ray diffraction) as well. This study clearly indicates that c3diPhe, a sterically demanding cyclopropane analogue of phenylalanine, tends to fold peptides into beta-turn and 3(10)-helix conformations. However, when c3diPhe is in combination with other chiral residues, the conformation preferred by the resulting peptides is also dictated by the chiral sequence of the amino acid building blocks. The (S,S)-enantiomer of this alpha-amino acid, unusually lacking asymmetry in the main chain, strongly favors the left-handedness of the turn/helical peptides formed.

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Turn and Helical Peptide Handedness Governed Exclusively by Side-Chain Chiral Centers

Cited by 58 publications

References 19 publications

Characterization of β‐turn and Asx‐turns mimicry in a model peptide: Stabilization via CH · · · O interaction

Characterization of β‐turn and Asx‐turns mimicry in a model peptide: Stabilization via CH · · · O interaction

Conformations of peptides containing a chiral cyclic α, α‐disubstituted α‐amino acid within the sequence of Aib residues

Preferred 3D‐Structure of Peptides Rich in a Severely Conformationally Restricted Cyclopropane Analogue of Phenylalanine

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