The critical main‐chain length for helix formation in water: Determined in a peptide series with alternating Aib and Ala residues exclusively and detected with ECD spectroscopy

Abstract

Critical main-chain length for peptide helix formation in the crystal (solid) state and in organic solvents has been already reported. In this short communication, we describe our results aiming at assessing the aforementioned parameter in water solution. To this goal, we synthesized step-by-step by solution procedures a complete series of N-terminally acetylated, C-terminally methoxylated oligopeptides, characterized only by alternating Aib and Ala residues, from the dimer to the nonamer level. All these compounds were investigated by electronic circular dichroism in the far-UV region in water solution as a function of chemical structure, namely presence/absence of an ester moiety or a negative charge at the C-terminus, and temperature. We find that the critical main-chain lengths for 3(10)- and α-helices, although still formed to a limited extent, in aqueous solution are six and eight residues, respectively.

Formation of bacterial pilus-like nanofibres by designed minimalistic self-assembling peptides

“…3c). A highly similar CD spectrum was previously reported for a sequential Aib-Alanine peptide which, based on the minima positions and the ratio of their intensities, was determined to be a partially folded α-helix58. The FTIR spectrum of the 12-mer contained an amide I band at 1,662 cm −1 (Fig.…”

1H‐Azepine‐4‐amino‐4‐carboxylic Acid: A New α,α‐Disubstituted Ornithine Analogue Capable of Inducing Helix Conformations in Short Ala‐Aib Pentapeptides

“…Furthermore, the Fmoc group can contribute in the far‐UV region with a positive peak below 214 nm, suggesting that the helical contents of both peptides could be underestimated 27. It should also be noted that previous studies on the conformational behavior of Ala‐Aib‐containing peptides have shown that a right‐handed 3 10 ‐helical structure usually first appears at the 7‐mer level in MeOH 5a. In the present case, we observed a helical conformation with a pentamer, suggesting that Azn has a strong helicogenic effect.…”

“…For these reasons, and considering that due to computational limitations we preferred implicit as opposed to explicit solvation, we decided to evaluate both the ff96 and the ff99SB force fields coupled with the igb=5 solvent model. Several sets of experimental data were available for Aib‐ and Ala‐containing peptides,5a, 6c,d but the 5‐mer Ala‐Aib‐Ala‐Aib‐Aib was particularly well suited for our testing because its crystal structure, evidencing a 3 10 ‐helical conformation, has been solved 6c. The N‐ and C‐termini were capped with acetyl (Ac) and NHMe groups instead of t Boc and OMe, respectively, as parameters for these residues are not present in the adopted force fields; the resulting model peptide is hereinafter referred to as P1.…”

Hydrophobic Aib/Ala peptides solubilize in water through formation of supramolecular assemblies

“…The terminally protected undecapeptide Z-(L-Ala) 3 -(Aib-L-Ala) 4 -OMe was prepared by solution synthesis, according to the procedures previously described. 2 4 -OH was obtained by treatment of its methyl ester precursor with a methanolic solution of LiOH, followed by protonation to -COOH with dilute HCl: infrared (KBr): 3323, 1663 and 1539 cm À1 ; electrospray ionization mass spectrometry m/z: calculated for C 45 H 71 N 11 O 14 990.13, found 990.10. The synthesis of the Au nanoparticles (AuNps11) used for the encapsulation experiments was previously reported.…”

“…After a careful inspection of all synthetic steps, we discovered that much of the product was lost in the purification procedures as, unexpectedly, these peptides are soluble in water. 1,2 To the best of our knowledge, this is the first example of a class of N-and C-terminally protected, hydrophobic peptides able to dissolve in water. This finding is even more surprising in view of the absence of any residue having a charged (for example, Lys and Asp) or a polar (for example, Ser and Thr) side chain.…”