<sup>1</sup>H and <sup>13</sup>C NMR studies of conformational behaviour of Leu‐enkephalin

Garbay‐Jaureguiberry, Christiane; Roques, Bernárd P.; Oberlin, R.

doi:10.1016/0014-5793(77)80128-2

Cited by 70 publications

(51 citation statements)

References 23 publications

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“…For analogues 20a-c and 21a-b with the D-and L-bicyclo moiety, extended structures were found at these two positions, also independent of the bridgehead stereochemistry. These findings rationalize the design and use of these bicyclic dipeptides in our study to mimic the different conformations reported [35][36][37][38][39][40] on Leu-enkephalin. However, it must be noted that the analogue (21c) with the same D-and L-bicyclo moiety gives a reverse turn structure instead of an extended structure.…”

Section: Conformational Studiessupporting

confidence: 79%

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Parallel synthesis and biological evaluation of different sizes of bicyclo^[2,3]‐Leu‐enkephalin analogues

Gu¹,

Ying²,

Min³

et al. 2005

Biopolymers

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Section: Conformational Studiessupporting

confidence: 79%

“…In previous conformational studies [35][36][37][38][39][40] on this endogenous neuropeptide, both turn and extended conformations spanning residues 2-3 were reported. Depending on the configurations of the chiral centers in the bicyclic dipeptides, these dipeptides may be constrained to different conformations.…”

Section: Conformational Studiesmentioning

confidence: 99%

Parallel synthesis and biological evaluation of different sizes of bicyclo^[2,3]‐Leu‐enkephalin analogues

Gu¹,

Ying²,

Min³

et al. 2005

Biopolymers

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“…On the other hand, the chemical shifts of the residues Tyr-1, Gly-3 and Phe-4 in (C2H3)2SO:'2H20 are strongly shielded in the trans form of peptide I as compared to those found for the corresponding residues in Met-enkephalin and Leu-enkephalin where they are almost identical [14,15]. This result also indicates the more puckered conformation of peptide I.…”

Section: I3c N M R Studies Of Peptides I and 11mentioning

confidence: 77%

“…The population of the rotamer gg' is small in the tyrosine residue in the two compounds in dimethylsulfoxide. This feature is quite general in enkephalin derivatives [37] and, in the light of the crucial role of the tyramine moiety in opiates, the excess of tg rotamers has been related to the activity of the opioid peptides [13,14].…”

Section: Side-chain Conformationsmentioning

confidence: 99%

“…Indeed the ratios < 2 have to be related to the presence of preferred conformations for the prolyl ring [49,50] in peptide I. Furthermore, no significant internal rotation of the aromatic ring of tyrosine seems to occur, as shown by the similarity in the N Z values for all the protonated carbons of the residue at variance with the NK values in Met-enkephalin or Leu-enkephalin [14,15] which indicate a fast reorientation around the C-a -C-i" axis, the N Z values found in cis and trans peptide I seem to indicate a preferential motion around the C-p-C-5 axis. This could be related to a restricted degree of freedom for the C-a-C-p carbons.…”

Section: I3c Relaxation Measurementsmentioning

confidence: 99%

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Studies of the Conformational Behaviour and Preferential Interactions with Opiate Receptors of the cis and trans Forms of [dMet2, Pro5]Enkephalin and [dMet2, Pro5]Enkephalinamide by 1H and 13C NMR, Theoretical Calculations and 13C Relaxation Measurements

Roques¹,

Garbay‐Jaureguiberry²,

Bajusz³

et al. 2005

European Journal of Biochemistry

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[DMet', Pro5]Enkephalin (I) and [DMet', Pro']enkephalinamide (11), two of the more potent opioid peptides, have been studied by 'H and I3C N M R and by theoretical calculations. Their biological activity is tentatively related to their conformational behaviour. A cis S trans equilibrium around the Phe-Pro bond is brought about by the terminal prolyl residue. The cisjtrans ratios lie around 50j50 for peptide I (55 cis in dimethylsulfoxide, 35 o/, cis in water) and around 20/80 for peptide 11, the more potent compound, in both the solvents. Almost all the signals, both in 'H and I3C spectra, give separate resonances for the cis and trans rotamers, in dimethylsulfoxide as well as in water. A temperature variation allows one to determine the rotational barrier (AG;, z 81.5 kJ/mol) for the cis $ trans interconversion. The analysis of the vicinal coupling constants and theoretical calculations suggests that Tyr-DMet-Gly-Phe-Pro exists as a class of highly puckered conformations with short end-to-end distances at r = 0.4 nm and r = 0.6 nm for the trans and cis configurations respectively. The populations of the side-chain rotamers are predominantly trans/gauche (tg) for the tyrosine residue. This feature, which is quite general in enkephalins, is related to the crucial role of the tyramine moiety for opioid activity. The orientation of the Phe-4 side-chain is independent of the spatial disposition of the following prolyl residue. pH titrations provide evidence for the existence of head-to-tail interactions. Hence, in ('H6)dimethylsulfoxide, and to a lesser extent in 'HzO, the titration of the Pro-5 residue is clearly felt on the Tyr-1 moiety, whereas the deprotonation of this latter residue leads to changes in the chemical shifts of the pyrrolidine ring protons. The B protons of the Tyr-1 and Phe-4 residues are strongly magnetically nonequivalent; the opposite is true for Met-enkephalin where they show the same chemical shifts below pH 6. The titration effects suggest that no strong conformational change occurs during the amino or carboxyl group titration and indicate an important steric hindrance on the N M R time scale for the two aromatic side chains.The 13C NMR spectra of peptide I in ('Hg)dimethylsulfoxide and in a mixture of ('H6)dimethylsulfoxidej'H20 (50/50) exhibit for almost all the resonances well-separated signals, corresponding to the cis and trans conformers. The large changes in I3C chemical shifts occurring Qn the backbone and side-chain carbons during the titration steps confirm the through-space effects already deduced from the proton titration curves. Hence, several C-a (Met-2, Phe-4) and C-p (Met-2, Pro-5) atoms are affected by both the titrations of the two terminal parts of the peptide. Such effects were not observed in Met-enkephalin or Leu-enkephalin. The I3C relaxation times for the cis and trans rotamers were compared, in ('H6)dimethylsulfoxide, under strictly the same conditions. All the NTl values are small and lie in the same range both for the carbons of the peptide backbone and for the ca...

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Conformational energy analysis of retro‐all‐Dmethionine enkephalin

Momany

AuBuchon

1978

Biopolymers

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SynopsisEmpirical conformational energy calculations have been carried out on the molecule retro-all-D-methionine enkephalin. Low-energy conformers were found by energy minimization and conformational search procedures. The lowest energy conformers were found to have some stereochemical relationship to the calculated normal met-enkephalin conformers, but they were not retro-all-D-equivalent to the Met-enkephalin structures. The retro-all-D-equivalent conformations were -10 kcdmol higher energy than the low-energy conformers found here. A structural comparison between the retro-all-D-conformers and the met-enkephalin conformers shows that one cannot rely solely on topochemical analysis to predict biological activity for linear retro-all-D-peptides.

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¹H and ¹³C NMR studies of conformational behaviour of Leu‐enkephalin

Cited by 70 publications

References 23 publications

Parallel synthesis and biological evaluation of different sizes of bicyclo^[2,3]‐Leu‐enkephalin analogues

Parallel synthesis and biological evaluation of different sizes of bicyclo^[2,3]‐Leu‐enkephalin analogues

Studies of the Conformational Behaviour and Preferential Interactions with Opiate Receptors of the cis and trans Forms of [dMet2, Pro5]Enkephalin and [dMet2, Pro5]Enkephalinamide by 1H and 13C NMR, Theoretical Calculations and 13C Relaxation Measurements

Conformational energy analysis of retro‐all‐Dmethionine enkephalin

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1H and 13C NMR studies of conformational behaviour of Leu‐enkephalin

Cited by 70 publications

References 23 publications

Parallel synthesis and biological evaluation of different sizes of bicyclo[2,3]‐Leu‐enkephalin analogues

Parallel synthesis and biological evaluation of different sizes of bicyclo[2,3]‐Leu‐enkephalin analogues

Studies of the Conformational Behaviour and Preferential Interactions with Opiate Receptors of the cis and trans Forms of [dMet2, Pro5]Enkephalin and [dMet2, Pro5]Enkephalinamide by 1H and 13C NMR, Theoretical Calculations and 13C Relaxation Measurements

Conformational energy analysis of retro‐all‐Dmethionine enkephalin

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Product

Resources

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¹H and ¹³C NMR studies of conformational behaviour of Leu‐enkephalin

Parallel synthesis and biological evaluation of different sizes of bicyclo^[2,3]‐Leu‐enkephalin analogues

Parallel synthesis and biological evaluation of different sizes of bicyclo^[2,3]‐Leu‐enkephalin analogues