Pal, S and Banerjee, S and Kumar, A and Prabhakaran, EN (2020) H-Bond Surrogate-Stabilized Shortest Single-Turn α-Helices: Sp2 Constraints and Residue Preferences for the Highest α-Helicities. In: ACS Omega, 5 (23). pp. 13902-13912.
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Abstract
Short α-helical sequences of proteins fail to maintain their native conformation when taken out of their protein context. Several covalent constraints have been designed, including the covalent H-bond surrogate (HBS) - where a peptide backbone i + 4 � i H-bond is replaced by a covalent surrogate - to nucleate α-helix in short sequences (>7 < 15 amino acids). But constraining the shortest sequences (four amino acids) into a single α-helical turn is still a significant challenge. Here, we introduce an HBS model that can be placed in unstructured tetrapeptides without excising any of its residues, and that biases them predominantly into remarkably stable single α-helical turns in varying solvents, pH values, and temperatures. Circular dichroism (CD), Fourier transform infrared (FT-IR) absorption, one-dimensional (1D)-NMR, two-dimensional (2D)-NMR spectral and computational analyses of the HBS-constrained tetrapeptide analogues reveal that (a) the number of sp2 atoms in the HBS-constrained backbone influences their predominance and rigidity in the α-helical conformation; and (b) residue preferences at the unnatural HBS-constrained positions influence their α-helicities, with MocGFAG-OMe (1a) showing the highest known α-helicity (θn�?*MRE ?-25.3 � 103 deg cm2 dmol-1 at 228 nm) for a single α-helical turn. Current findings benefit chemical biological applications desiring predictable access to single α-helical turns in tetrapeptides. © 2020 American Chemical Society.
| Item Type: | Journal Article |
|---|---|
| Publication: | ACS Omega |
| Publisher: | American Chemical Society |
| Additional Information: | Copy right for this article belongs to American Chemical Society |
| Department/Centre: | Division of Chemical Sciences > Organic Chemistry |
| Date Deposited: | 26 Nov 2020 10:39 |
| Last Modified: | 26 Nov 2020 10:39 |
| URI: | http://eprints.iisc.ac.in/id/eprint/65819 |
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