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Peptide conformations. Part 30 . Assignment of the 1 H‐, 13 C‐, and 15 N‐NMR spectra of cyclosporin A in CDCl 3 and C 6 D 6 by a combination of homo‐ and heteronuclear two‐dimensional techniques
Author(s) -
Kessler Horst,
Loosli HansRudolf,
Oschkinat Hartmut
Publication year - 1985
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19850680318
Subject(s) - chemistry , heteronuclear molecule , proton , amide , yield (engineering) , nmr spectra database , spectral line , pulse sequence , two dimensional nuclear magnetic resonance spectroscopy , coupling constant , nuclear magnetic resonance spectroscopy , crystallography , stereochemistry , proton nmr , carbon 13 nmr satellite , chemical shift , nuclear overhauser effect , spectroscopy , nuclear magnetic resonance , fluorine 19 nmr , physics , organic chemistry , quantum mechanics , astronomy , particle physics , thermodynamics
Abstract The 1 H‐, 13 C‐, and 15 N‐NMR spectra of the immunosuppressive cyclic undecapeptide cyclosporin A ( 1 ) have been analyzed at 300 MHz in CDCl 3 , C 6 D 6 , and mixtures of these solvents. A combination of different homo‐ and heteronuclear two‐dimensional NMR techniques enable complete assignment of all H‐, C‐ and 4 N‐signals. Recognition of the proton spin systems has been achieved via 1 H, 1 H–COSY and double‐quantum‐ 1 H‐NMR spectroscopy. NOESY spectra yield some sequence assignments, but two techniques using coupling across amide bonds have been applied to get independent assignments of all amino acids in the sequence: ( i ) An 1 H, 1 H‐COSY spectrum optimized for small coupling constants enables the detection of long‐range couplings from N ‐methyl groups to both α‐protons attached to that amide bond. ( ii ) An 1 H, 13 C‐COSY spectrum optimized for C,H‐long‐range couplings ( J = 5 to 10 Hz) to the eleven CO groups again yields coupling to both α‐protons attached to that amide bond. Additionally these two experiments yield the assignment of N ‐methyl protons and carbonyl C‐atoms. Normal and relayed 1 H, 13 C‐COSY in both solvents have been applied to assign all C‐atoms via their directly attached and remote protons. An 1 H, 13 C‐COLOC spectrum at 500 MHz in CDCl 3 , which uses H,C‐long‐range couplings confirms the assignment of all proton spin systems as well as the C‐signals of each individual amino acid. Ambiguities in the assignment of the C(δ)'s of MeLeu have thus been removed. An 1 H, 15 N‐COSY spectrum enables the assignment of the 4 NH N‐atoms.