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17 O‐nmr studies of the conformational and dynamic properties of enkephalins in aqueous and organic solutions using selectively labeled analogues
Author(s) -
Sakarellos Constantinos,
Gerothanassis Ioannis P.,
Birlirakis Nicolaos,
Karayannis Theodoros,
SakarellosDaitsiotis Maria,
Marraud Michel
Publication year - 1989
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360280105
Subject(s) - chemistry , chemical shift , protonation , hydrogen bond , aqueous solution , solvent , peptide , enkephalin , hydrogen , crystallography , stereochemistry , oxygen , molecule , organic chemistry , ion , biochemistry , receptor , opioid
The synthesis of Leu‐enkephalin selectively 17 O‐enriched in Gly 2 and Gly 3 is reported. The 17 O‐nmr chemical shifts of [ 17 O‐Gly 2 , Leu 5 ]‐ and [ 17 O‐Gly 3 , Leu 5 ]‐enkephalins in H 2 O are almost identical and independent of the pH. Since hydrogen bonding is the dominant factor governing the chemical shifts of the peptide oxygen, it can be concluded that the hydration state of both oxygens is identical and independent of the pH. The 17 O chemical shifts of the [ 17 O‐Leu 5 ]‐enkephalin terminal carboxyl group at pH ∼ 1.9 and 5.6 are very different in H 2 O but very similar in CH 3 CN/DMSO (4:1) solution. This suggests that the protonation state of the carboxyl group at both pH values in CH 3 CN/DMSO solution is the same and consequently that Leu‐enkephalin exists in the neutral form at pH ∼ 5.6. In this organic mixed solvent system both Gly 2 and Gly 3 oxygen resonances exhibit a significant shift to high frequency by the same extent (Δδ ∼ 30 ppm). It is concluded that both peptide oxygens are not hydrogen bonded to an appreciable extent and that no specific 2 ← 5 hydrogen bonding exists to an appreciable extent. This conclusion is in agreement with the energy of activation for molecular rotation, as determined from T 1 measurements, which was found to be almost identical for both [ 17 O‐Gly 2 , Leu 5 ]‐ and [ 17 O‐Gly 3 , Leu 5 ]‐enkephalins in CH 3 CN/DMSO (4:1) mixed solvent.