Details

Autor(en) / Beteiligte

• Debnath, Swapna
• Vignesh, S. R.
• Satpati, Priyadarshi
• Chatterjee, Sunanda

Titel

Position of Geminal Substitution of γ Amino Acid Residues Modulates Their Ability to Form Isolated Non‐Helical C12 β‐turn Mimics

Ist Teil von

• ChemistrySelect (Weinheim), 2023-02, Vol.8 (7), p.n/a

Erscheinungsjahr

2023

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• We have attempted the construction of isolated αγ non‐helical C12 β‐turn mimics in Boc‐Val‐DPro‐γx,x‐Leu‐NHMe (x,x=2/2, 3/3, 4/4) peptides by the incorporation of differentially dimethyl substituted γ amino acid residues at the (i+2) position of the turn. Solution conformation was probed in detail using NMR and CD spectroscopy. Irrespective of the solvent polarity, peptide containing γ2,2 amino acid residues failed to form the isolated tight β‐turn mimetic while peptides containing γ3,3 and γ4,4 residues successfully adopted isolated non‐helical C12 β‐turn mimic structure. The conformations adopted in solution were corroborated with DFT calculations. Such difference in the stereochemical ability of these di‐substituted γ amino acid residues arose from the difference in position of the di‐substitution along the backbone of the residue. Thus prudent choice of the position of di‐substitution in ω amino acid residues might be used as a strong peptidomimetic handle to control the structural design and generate complex structures. Differential position of geminal di‐substitution in γ amino acid residues, constrains their backbone differently and controls their ability to be accommodated at the (i+2) position of isolated C12 non‐helical β‐turn mimics. Only γ3,3 and γ4,4 can give rise to tight turns while, γ2,2 form a bent structure across DPro‐γx,x segment.