Helicalversus Planar Conformation of Homooligopeptides Prepared from Diethylglycine (=2-Amino-2-ethylbutanoic Acid)

Tanaka, Masakazu; Imawaka, Naoto; Kurihara, Masaaki; Shimizu, Hiroshi

doi:10.1002/(sici)1522-2675(19990407)82:4<494::aid-hlca494>3.0.co;2-a

Cited by 34 publications

(57 citation statements)

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“…Moreover, an explanation for the published crystallographic results on the terminally protected homo‐pentapeptide sequence from Deg (C α,α ‐diethyl glycine) (Figure ), a C α ‐tetrasubstituted residue generally considered the simplest one of the subclass largely favoring the fully‐extended conformation, is not clear‐cut (Figure ). Indeed, the originally reported 3D‐structure of the Tfa (trifluoroacetyl)/O t Bu ( tert ‐butyloxy) terminally protected ‐(Deg) 5 ‐ was found to adopt the fully extended conformation, whereas that of Tfa‐(Deg) 5 ‐OEt (OEt, ethoxy), published years later, is 3 10 ‐helical . Interestingly, this latter observation was recently corroborated by the results of two additional X‐ray diffraction analyses, specifically on Ac‐(Deg) 5 ‐O t Bu tetrahydrofuran solvate and PyrAc‐(Deg) 5 ‐O( p NO 2 )Bzl, where PyrAc is 1‐pyrenylacetyl and O( p NO 2 )Bzl is para ‐nitrobenzyloxy.…”

Section: Brief Summary On Peptides Before 2012mentioning

confidence: 70%

The fully‐extended conformation in peptides and proteins

et al. 2018

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The intramolecularly H‐bonded, fully‐extended conformation (C5) of an α‐amino acid residue (and the resulting 2.05‐helix obtained via its propagation) is one of the least extensively investigated types of peptide and protein backbone secondary structure. This situation does still currently occur despite its unique ability to enjoy by far the largest separation per residue among peptide conformations. In this article, we offer a detailed update of our present knowledge on this intriguing 3D‐structure of peptides in the crystal state as obtained from recently published investigations, complemented by a statistical analysis for its occurrence in the crystal structures of α‐amino acid derivatives and peptides available in the Cambridge Structural Database. We have expanded this useful information to the results of a bioinformatics analysis performed on this (so far largely unappreciated) conformation authenticated in all proteins solved by X‐ray diffraction to a resolution of ≤ 1.5 Å. In the last section, we describe the results of our DFT calculations on the conformational preferences of a set of homopeptides (from monomer to octamer) based on as many as six proteins and two noncoded, carefully selected, α‐amino acids. From this literature survey integrated by new energy calculations, we have definitely provided strong support to the thesis that this polypeptide 3D‐structure does indeed exist, it should be not neglected in future studies by structural biochemists, and it represents a very attractive, novel backbone for applications for organic, medicinal, and biomaterials chemists.

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Section: Brief Summary On Peptides Before 2012mentioning

confidence: 70%

The fully‐extended conformation in peptides and proteins

et al. 2018

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“…The Abu conformational preferences are very similar to those featured by standard amino acids with similar constitution (such as Val, Ile, or Leu) 36, 37. Interestingly, this amino acid critically affects the 2.0 5 ‐helix adopted both in solvents of low polarity and in the crystal state by the aforementioned Deg homopentapeptide 38–40. Specifically, Tfa‐(Deg) 2 ‐ L ‐Abu‐(Deg) 2 ‐O t Bu folds into a 3 10 ‐helix in the crystal state, while in solution the spectroscopic information points to an increase of the population of folded conformers as compared to that of the parent homopeptide 35…”

Section: Introductionmentioning

confidence: 68%

Correlation between symmetry breaker position and the preferences of conformationally constrained homopeptides: A molecular dynamics investigation

et al. 2008

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The conformational tendencies of C(alpha,alpha)-diethylglycine (Deg)-based peptides have been studied in solution using all atom molecular dynamics simulations. Specifically, the conformational effects of breaking the symmetry of the host Tfa-(Deg)(5)-OtBu (Tfa, trifluoroacetyl; OtBu, tert-butoxy) pentapeptide with punctual replacements at different sequence positions of one Deg residue by its corresponding guest chiral analogue, L-alpha-aminobutyric acid (L-Abu), have been examined by simulating the following peptides: Tfa-(Deg)(5)-OtBu, Tfa-(Deg)(2)-L-Abu-(Deg)(2)-OtBu, Tfa-(Deg)(3)-L-Abu-Deg-OtBu, and Tfa-(Deg)(4)-L-Abu-OtBu. Simulations show that only the Deg homopeptide is able to stabilize a 2.0(5) helix, even though a kinked arrangement with all the Deg residues adopting a fully-extended conformation was found to be stable when the L-Abu residue is introduced in the middle of the sequence. On the other hand, when the L-Abu residue is closer to the C-end of the sequence, the peptide chain prefers a partially folded 3(10)-helix. Additional simulations on Tfa-(Deg)(3)-L-Abu-(Deg)(3)-OtBu highlighted that, when the size of the Deg segments increases, their tendency to adopt a 2.0(5) helix predominates over the preferred folded conformation of L-Abu. The overall picture extracted after more than 300 ns of molecular dynamics simulation is that breaking the alpha-carbon symmetry of achiral C(alpha)-tetrasubstituted amino acids is a promising strategy to build up polypeptides with modulated conformational tendencies.

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“…4). [12][13][14] The extended C 5 -conformation is an extended planar conformation of the peptide-backbone, showing two torsion angles of fϭ180°, jϭ180°. Achiral homopeptides composed of dipropylglycine, dibutylglycine, or diphenylglycine also preferentially form the extended conformation.…”

Section: Secondary Structures Of Peptides Composed Of a Aa Adisubstimentioning

confidence: 99%

“…The olefin function in the amino acid (12) could be hydrogenated to afford saturated bicyclic amino acid (13), and also could be ozonolized to produce various cyclic amino acids. After the ozonolysis of olefin, reduction with NaBH 4 afforded a cyclic amino acid (14) having a hydroxyl function, oxidation gave an amino acid (15) with a dicarboxylic acid moiety, and reductive amination with BnNH 2 and NaBH 3 CN produced a bicyclic amino acid (16) having a 7-membered ring.…”

Section: Design and Synthesis Of A Chiral Bicyclic A Aa A-disubstitumentioning

confidence: 99%

Design and Synthesis of Chiral .ALPHA.,.ALPHA.-Disubstituted Amino Acids and Conformational Study of Their Oligopeptides

Tanaka

2007

Chem. Pharm. Bull.

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Helicalversus Planar Conformation of Homooligopeptides Prepared from Diethylglycine (=2-Amino-2-ethylbutanoic Acid)

Cited by 34 publications

References 0 publications

The fully‐extended conformation in peptides and proteins

The fully‐extended conformation in peptides and proteins

Correlation between symmetry breaker position and the preferences of conformationally constrained homopeptides: A molecular dynamics investigation

Design and Synthesis of Chiral .ALPHA.,.ALPHA.-Disubstituted Amino Acids and Conformational Study of Their Oligopeptides

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