Helix packing motif common to the crystal structures of two undecapeptides containing dehydrophenylalanine residues: Implications for the de novo design of helical bundle super secondary structural modules

Dehydroamino acids are non-coded amino acids that offer unique conformational properties. Dehydrophenylalanine (DeltaPhe) is most commonly used to modify bioactive peptides to constrain the topography of the phenyl ring in the side chain, which commonly serves as a pharmacophore. The Ramachandran maps (in the gas phase and in CHCl(3) mimicking environments) of DeltaPhe analogues with methyl groups at the beta position of the side chain as well as at the C-terminal amide were calculated using the B3LYP/6-31 + G** method. Unexpectedly, beta-methylation alone results in an increase of conformational freedom of the affected DeltaPhe residue. However, further modification by introducing an additional methyl group at C-terminal methyl amide results in a steric crowding that fixes the torsion angle psi of all conformers to the value 123 degrees , regardless of the Z or E position of the phenyl ring. The number of conformers is reduced and the accessible conformational space of the residues is very limited. In particular, (Z)-Delta(betaMe)Phe with the tertiary C-terminal amide can be classified as the amino acid derivative that has a single conformational state as it seems to adopt only the beta conformation.

Section: Introductionmentioning

confidence: 99%

The effect of β‐methylation on the conformation of α, β‐dehydrophenylalanine: a DFT study

Broda

Buczek

Siodłak

et al. 2009

“…The crystal structures of three 11‐mer peptides with the sequence Ac‐Gly‐ l ‐Ala‐Δ Z Phe‐( l ‐Leu‐Xxx‐Δ Z Phe) 2 ‐ l ‐Ala‐Gly‐NH 2 , where the Xxx dyads are formed by l ‐Val or l ‐Ala or Gly, differ substantially. While those with the ‘ l ‐Val’ or ‘ l ‐Ala’ central residues reveal the expected right‐handed 3 10 ‐helical conformations , those with the two ‘Gly’ residues in the middle of the sequence adopt a 3 10 ‐helix of ambidextrous screw sense with two molecules arranged antiparallely . Interestingly, in the packing mode of the l ‐Val and l ‐Ala peptides, a given helix is surrounded by six other helices.…”

Section: Cαβ‐didehydro‐α‐amino Acid‐containing Peptidesmentioning

confidence: 98%

“…Induced CD proved to be an excellent tool to determine the solution conformation of peptides based on the achiral ΔPhe residue, especially in detecting the screw sense of the helices formed. It is principally for this reason that the number of publications on this topic is huge . The Δ Z Phe‐containing peptides show different CD curves in the near‐UV region depending on the main‐chain length and on the position in the sequence and number of the Δ Z Phe residues.…”

Section: Cαβ‐didehydro‐α‐amino Acid‐containing Peptidesmentioning

confidence: 99%

See 1 more Smart Citation

Handedness preference and switching of peptide helices. Part II: Helices based on noncodedα‐amino acids

Crisma¹,

Zotti

Formaggio

et al. 2015

In this second part of our review article on the preferred screw sense and interconversion of peptide helices, we discuss the most significant computational and experimental data published on helices formed by the most extensively investigated categories of noncoded α-amino acids. They are as follows: (i) N-alkylated Gly residues (peptoids), (ii) C(α) -alkylated α-amino acids, (iii) C(α,β) -sp(2) configurated α-amino acids, and (iv) combinations of residues of types (ii) and (iii). With confidence, the large body of interesting papers examined and classified in this editorial effort will stimulate the development of helical peptides in many diverse areas of biosciences and nanosciences.

“…A notable number of consecutive ΔPhecontaining structures have been shown to adopt the 3 10 -helix of both screw senses [22][23][24]. The potential of ΔPhe in achieving desired folding of super-secondary structural motifs including helix-turn-helix [5,25], helical bundle [26] and glycine zipper [27] has been amply demonstrated.…”

Section: Introductionmentioning

confidence: 99%

De novo design, synthesis and solution conformational study of two didehydroundecapeptides: effect of nature and number of amino acids interspersed between Phe residues

Dutta

Mathur

Chauhan

2011

De novo design of peptides and proteins has recently surfaced as an approach for investigating protein structure and function. This approach vitally tests our knowledge of protein folding and function, while also laying the groundwork for the fabrication of proteins with properties not precedented in nature. The success relies heavily on the ability to design relatively short peptides that can espouse stable secondary structures. To this end, substitution with α,β-didehydroamino acids, especially α,β-didehydrophenylalanine (Δ(z)Phe), comes in use for spawning well-defined structural motifs. Introduction of ΔPhe induces β-bends in small and 3(10)-helices in longer peptide sequences. The present work aims to investigate the effect of nature and the number of amino acids interspersed between two ΔPhe residues in two model undecapeptides, Ac-Gly-Ala-ΔPhe-Ile-Val-ΔPhe-Ile-Val-ΔPhe-Ala-Gly-NH(2) (I) and Boc-Val-ΔPhe-Phe-Ala-Phe-ΔPhe-Phe-Leu-Ala-ΔPhe-Gly-OMe (II). Peptide I was synthesized using solid-phase chemistry and characterized using circular dichroism spectroscopy. Peptide II was synthesized using solution-phase chemistry and characterized using circular dichroism and nuclear magnetic resonance spectroscopy. Peptide I was designed to examine the effect of incorporating β-strand-favoring residues like valine and isoleucine as spacers between two ΔPhe residues on the final conformation of the resulting peptide. Circular dichroism studies on this peptide have shown the existence of a 3(10)-helical conformation. Peptide II possesses three amino acids as spacers between ΔPhe residues and has been reported to adopt a mixed 3(10)/α-helical conformation using circular dichroism and nuclear magnetic resonance spectroscopy studies.