1. Hybrid peptide design. Hydrogen bonded conformations in peptides containing the stereochemically constrained gamma-amino acid residue, gabapentin
Prema G Vasudev, Kuppanna Ananda, Sunanda Chatterjee, Subrayashastry Aravinda, Narayanaswamy Shamala, Padmanabhan Balaram J Am Chem Soc. 2007 Apr 4;129(13):4039-48. doi: 10.1021/ja068910p. Epub 2007 Mar 10.
The crystal structure of 12 peptides containing the conformationally constrained 1-(aminomethyl)cyclohexaneacetic acid, gabapentin (Gpn), are reported. In all the 39 Gpn residues conformationally characterized so far, the torsion angles about the Calpha-Cbeta and Cbeta-Cgamma bonds are restricted to the gauche conformation (+/-60 degrees ). The Gpn residue is constrained to adopt folded conformations resulting in the formation of intramolecularly hydrogen-bonded structures even in short peptides. The peptides Boc-Ac6c-Gpn-OMe 1 and Boc-Gpn-Aib-Gpn-Aib-OMe 2 provide examples of C7 conformation; peptides Boc-Gpn-Aib-OH 3, Boc-Ac6c-Gpn-OH 4, Boc-Val-Pro-Gpn-OH 5, Piv-Pro-Gpn-Val-OMe 6, and Boc-Gpn-Gpn-Leu-OMe 7 provide examples of C9 conformation; peptide Boc-Ala-Aib-Gpn-Aib-Ala-OMe 8 provides an example of C12 conformation and peptides Boc-betaLeu-Gpn-Val-OMe 9 and Boc-betaPhe-Gpn-Phe-OMe 10 provide examples of C13 conformation. Gpn peptides provide examples of backbone expanded mimetics for canonical alpha-peptide turns like the gamma (C7) and the beta (C10) turns. The hybrid betagamma sequences provide an example of a mimetic of the C13 alpha-turn formed by three contiguous alpha-amino acid residues. Two examples of folded tripeptide structures, Boc-Gpn-betaPhe-Leu-OMe 11 and Boc-Aib-Gpn-betaPhg-NHMe 12, lacking internal hydrogen bonds are also presented. An analysis of available Gpn residue conformations provides the basis for future design of folded hybrid peptides.
2. Correlations between steric/thermochemical parameters and O-/N-acylation reactions of cellulose
Kesavan Devarayan, Taketoshi Hayashi, Masakazu Hachisu, Jun Araki, Kousaku Ohkawa Carbohydr Polym. 2013 Apr 15;94(1):468-78. doi: 10.1016/j.carbpol.2012.12.074. Epub 2013 Jan 16.
N(α)-t-Butyloxycarbonyl (Boc)-amino acids (Xaa = Gly, Ala, or β-Ala) were reacted with the cellulose hydroxyl groups (O-acylation) using N,N'-carbonyl diimidazole. The degrees of substitution toward the total hydroxyl groups (DS%(/OH)s) were 38% for O-(Boc-Gly)-Cellulose, 29% for O-(Boc-Ala)-Cellulose and 53% for O-(Boc-β-Ala)-Cellulose. The one-by-one N-acylation between the O-(Xaa)-Celluloses and Boc-Ala-Gly using a water-soluble carbodiimide yielded the conjugates N-(Boc-Ala-Gly)-Xaa-Celluloses with DS%(/NH2) values of 25% (Xaa = Gly), 35% (Ala), and 48% (β-Ala), respectively. The results were well correlated with ΔG and ΔEstrain profiles, which were predicted by semi-empirical thermochemical parameter calculation coupled with conformer search (R(2)>0.90). N-acylation of the O-(β-Ala)-Cellulose using various length of oligo-peptides, Boc-(Ala-Gly)n and Boc-(Gly-Ala)n (where, n = 0.5, 1.0, 1.5, 2.0, 3.0), suggested that the DS%(/NH2) was dependent on the structural features of the symmetric anhydrides as the N-acylating agents, including conformer populations and their transition energy.
3. [Peptide derivatives of tylosin-related macrolides]
G A Korshunova, N V Sumbatian, N V Fedorova, I V Kuznetsova, A V Shishkina, A A Bogdanov Bioorg Khim. 2007 Mar-Apr;33(2):235-44. doi: 10.1134/s1068162007020033.
Approaches to the synthesis of model compounds based on the tylosin-related macrolides desmycosin and O-mycaminosyltylonolide were developed using specially designed peptide derivatives of macrolide antibiotics to study the conformation and topography of the nascent peptide chain in the ribosome tunnel. A method for selective bromoacetylation of desmycosin at the hydroxyl group of mycinose was developed, which involves preliminary acetylation of mycaminose. The reaction of the 4"-bromoacetyl derivative of the antibiotic with cesium salts of the dipeptide Boc-Ala-Ala-OH and the hexapeptide MeOTr-Gly-Pro-Gly-Pro-Gly-Pro-OH led to the corresponding peptide derivatives of desmycosin. The protected peptides Boc-Ala-Ala-OH, Boc-Ala-Ala-Phe-OH, and Boc-Gly-Pro-Gly-Pro-Gly-Pro-OH were condensed with the C23-hydroxyl group of O-mycaminosyltylonolide.
