De Novo Design and Synthesis of Helix–Turn–Helix Structure from Short and Robust Mixed Helices Derived from C‐Linked Carbo‐β‐Amino Acids

Sharma, G. V. M.; Subash, Velaparthi; Narsimulu, K.; Sankar, A. Ravi; Kunwar, A. C.

doi:10.1002/ange.200603084

Cited by 4 publications

(12 citation statements)

References 19 publications

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“…Furthermore, this study also established the generality of the new turns with the incorporation of several α‐ and β‐amino acid residues in the turn region to generate HT and HTH motifs. This report, along with our recent design of HTH motifs,12 provides options to form a variety of tertiary structures, referred to as “tyligomers” by Moore and co‐workers,13 from hybrid peptides with a very large pool of helices, sheets, and turn motifs in the foldamer domain. We therefore cautiously and optimistically approach the moment when a glimpse in the wide horizon of designed artificial proteins is permitted, with various functional groups appropriately decorated in such scaffolds derived from foldamers and tyligomers.…”

Section: Discussionmentioning

confidence: 99%

Three‐Residue Turns in α/β‐Peptides and Their Application in the Design of Tertiary Structures

Sharma

Pendem

Ramakrishna

et al. 2008

Chemistry An Asian Journal

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A new three-residue turn was serendipitously discovered in alpha/beta hybrid peptides derived from alternating C-linked carbo-beta-amino acids (beta-Caa) and L-Ala residues. The three-residue beta-alpha-beta turn at the C termini, nucleated by a helix at the N termini, resulted in helix-turn (HT) supersecondary structures in these peptides. The turn in the HT motif is stabilized by two H bonds-CO(i-2)-NH(i), with a seven-membered pseudoring (gamma turn) in the backward direction, and NH(i-2)-CO(i), with a 13-membered pseudoring in the forward direction (i being the last residue)--at the C termini. The study was extended to generalize the new three-residue turn (beta-alpha-beta) by using different alpha- and beta-amino acids. Furthermore, the HT motifs were efficiently converted, by an extension with helical oligomers at the C termini, into peptides with novel helix-turn-helix (HTH) tertiary structures. However, this resulted in the destabilization of the beta-alpha-beta turn with the concomitant nucleation of another three-residue turn, alpha-beta-beta, which is stabilized by 11- and 15-membered bifurcated H bonds. Extensive NMR spectroscopic studies were carried out to delineate the secondary and tertiary structures in these peptides, which are further supported by molecular dynamics (MD) investigations.

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Section: Discussionmentioning

confidence: 99%

Three‐Residue Turns in α/β‐Peptides and Their Application in the Design of Tertiary Structures

Sharma

Pendem

Ramakrishna

et al. 2008

Chemistry An Asian Journal

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“…showed distinct maxima at about 202 nm, with positive molar ellipticity (q) values above 195 nm, which is consistent with a 12/10-helix. [26,28,35] These results, as indicated from the NMR spectroscopic studies, show that as the b-hGly sequence becomes longer, the value of q decreases, which implies that integrity of the helical folds is being challenged and, thus, the robustness of the 12/10-helix is compromised.…”

Section: Wwwchemeurjorgmentioning

confidence: 90%

“…Base hydrolysis [4 n NaOH (aq)] of ester 26 gave acid 26 a, which furnished tripeptide 12 (87 %) on peptide coupling with salt 20. [28] Further peptide coupling of acid 16 with salt 27 a gave tetrapeptide 28 (71 %), which afforded salt 28 a after treatment with CF 3 COOH in CH 2 Cl 2 . Peptide coupling of acid 17 a with salt 27 a furnished pentapeptide 29 (70 %).…”

Section: Synthesis Of Peptides 4-7mentioning

confidence: 99%

“…The above facts, as well as several discrete medium-range nOe correlations [for example, CbH (1) (5), and NH(4)/NH (5), provide emphatic support for the presence of a 12/10-helix. [26,28] These findings are very important; they not only provide unmistakable evidence for the induction of a helical preference in achiral peptides, but also provide the first unequivocal experimental proof for the theoretically predicted preference for the 12/ 10-helix in b-peptides in apolar solvents. [20,21] MD calculations were undertaken by using the distance constraints obtained from the ROESY data, and two spin approximations were employed.…”

Section: Synthesis Of Peptidesmentioning

confidence: 99%

“…Although the populations of the major isomers increased substantially when both the peptide termini were anchored with (R)-b-Caa, all of the peptides studied above showed the presence of sizeable populations of other structures. Consequently, we decided to explore helix motif 12, [28] based on the concept of hybrid helices, for the induction of enhanced helical propensities in b-hGly oligomers and prepared peptides 13-15. For peptide 13, a highly dispersed 1 H NMR spectrum [32] infers the existence of a well-defined structure. The ROESY spectrum displayed several exchange peaks that implied the presence of two isomers.…”

Section: Wwwchemeurjorgmentioning

confidence: 99%

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Chirality and Template‐Mediated Induction of Helical Preferences in Achiral β‐Peptides

Sharma

Kodeti

Dutta

et al. 2012

Chemistry A European J

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This study describes chirality- or template-mediated helical induction in achiral β-peptides for the first time. A strategy of end capping β-peptides derived from β-hGly (the smallest achiral β-amino acid) with a chiral β-amino acid that possesses a carbohydrate side chain (β-Caa; C-linked carbo β-amino acid) or a small, robust helical template derived from β-Caas, was adopted to investigate folding propensity. A single chiral (R)-β-Caa residue at the C- or N-terminus in these oligomers led to a preponderance of right-handed 12/10-helical folds, which was reiterated more strongly in peptides capped at both the C- and N-terminus. Likewise, the presence of a template (a 12/10-helical trimer) at both the C- and N-terminus resulted in a very robust helix. The propagation of the helical fold and its sustenance was found in a homo-oligomeric sequence with as many as seven β-hGly residues. In both cases, the induction of helicity was stronger from the N terminus, whereas an anchor at the C terminus resulted in reduced helical propensity. Although these oligomers have been theoretically predicted to favor a 12/10-mixed helix in apolar solvents, this study provides the first experimental evidence for their existence. Diastereotopicity was found in both the methylene groups of the β-hGly moieties due to chirality. Additionally, the β-hGly units have shown split behavior in the conformational space to accommodate the 12/10-helix. Thus, end capping to assist chiralty- or template-mediated helical induction and stabilization in achiral β-peptides is a very attractive strategy.

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Three‐Residue Turn in β‐Peptides Nucleated by a 12/10 Helix

Sharma¹,

Yadav²,

Marumudi³

et al. 2014

Chemistry An Asian Journal

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A new three-residue turn in β peptides nucleated by a 12/10-mixed helix is presented. In this design, β peptides were derived from the 1:1 alternation of C-linked carbo-β-amino acid ester [BocNH-(R)-β-Caa(r)-OMe] (Boc=tert-butyloxycarbonyl), which consisted of a D-ribo furanoside side chain, and β-hGly residues. The hexapeptide with (R)-β-Caa(r) at the N terminus showed the 'turn' stabilized by a 14-membered NH(4)⋅⋅⋅CO(6) hydrogen bond at the C terminus nucleated by a robust 12/10-mixed helix, thus providing a 'helix-turn' (HT) motif. The turn and the helix were additionally stabilized by intraresidue electrostatic interaction between the furan oxygen in the carbohydrate side chain and NH in the backbone. However, the hexapeptide with a β-hGly residue at the N terminus demonstrated the presence of a 10/12 helix through its entire length, which again showed the intraresidue interaction between NH and furan oxygen. The intraresidue NH⋅⋅⋅O-Me electrostatic interactions observed in the monomer, however, were absent in the peptides.

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De Novo Design and Synthesis of Helix–Turn–Helix Structure from Short and Robust Mixed Helices Derived from C‐Linked Carbo‐β‐Amino Acids

Cited by 4 publications

References 19 publications

Three‐Residue Turns in α/β‐Peptides and Their Application in the Design of Tertiary Structures

Three‐Residue Turns in α/β‐Peptides and Their Application in the Design of Tertiary Structures

Chirality and Template‐Mediated Induction of Helical Preferences in Achiral β‐Peptides

Three‐Residue Turn in β‐Peptides Nucleated by a 12/10 Helix

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