title: Cis-Trans Conformational Analysis of δ-Azaproline in Peptides.
abstract: The cis-trans isomerization and conformer specificity of δ-azaproline and its carbamate-protected form in linear and cyclic peptides were investigated using NMR and α-chymotrypsin assay. Comparisons of the chemical shift value of the α-hydrogen in each case of δ-azaproline-containing peptides with conformer-specific locked diketopiperazines reveal the fact that an upfield chemical shift value corresponds to cis conformer and a downfield value corresponds to a trans conformer. δ-Azaproline adopts cis-conformation in simple amides, dipeptides, and tripeptides whereas its carbamate-protected form adopts trans-conformation. In the case of longer, linear or cyclic peptides, vice versa results are obtained. Interestingly, in all these peptides exclusively one conformer, either cis or trans, is stabilized. This cis-trans isomerization is independent of both temperature and solvents; only the δ-nitrogen protecting group plays key role in the isomerization. δ-Azaproline is conformer-specific in either of its protected or deprotected forms, which is a unique property of this proline. Unlike other covalently modified proline surrogates, this isomerization of δ-azaproline can be tuned easily by a protecting group. The mechanism of cis-trans isomerization of δ-azaproline during deprotection and reprotection is supported by theoretical calculations.
authors.affiliation: Department of Organic Chemistry and ‡Raman Centre for Atomic, Optical and Molecular Physics, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700 032, India.
authors.forename: Indranil
authors.initials: I
authors.lastname: Duttagupta
authors.affiliation: Department of Organic Chemistry and ‡Raman Centre for Atomic, Optical and Molecular Physics, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700 032, India.
authors.forename: Debojyoti
authors.initials: D
authors.lastname: Misra
authors.affiliation: Department of Organic Chemistry and ‡Raman Centre for Atomic, Optical and Molecular Physics, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700 032, India.
authors.forename: Sourav
authors.initials: S
authors.lastname: Bhunya
authors.affiliation: Department of Organic Chemistry and ‡Raman Centre for Atomic, Optical and Molecular Physics, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700 032, India.
authors.forename: Ankan
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Organic Chemistry and ‡Raman Centre for Atomic, Optical and Molecular Physics, Indian Association for the Cultivation of Science , Jadavpur, Kolkata 700 032, India.
authors.forename: Surajit
authors.initials: S
authors.lastname: Sinha
mesh_terms: D002918:Chymotrypsin / Q000737:chemistry*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D013816:Thermodynamics
chemical_list: D010455:Peptides; D011392:Proline; D002918:Chymotrypsin; C117608:alpha-chymotrypsin