Peptide conformations. 20. Conformational analysis of proline rings from proton spin-spin coupling constants and force-field calculations: application to three cyclic tripeptides

Leeuw, Frans L.; Altona, C.; Kessler, Horst; Bermel, Wolfgang; Friedrich, Axel; Krack, Gerhard; Hull, William E.

doi:10.1021/ja00346a023

Cited by 57 publications

(40 citation statements)

References 2 publications

(3 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such a correlation has been observed in cyclic tripeptides [42] and was in accord with force-field calculations [43]. In the case of 1 we found no correlation.…”

Section: Ala-8supporting

confidence: 91%

Peptide conformations. Part 31. The conformation of cyclosporin a in the crystal and in solution

Loosli¹,

Kessler²,

Oschkinat³

et al. 1985

Helvetica Chimica Acta

Self Cite

347

265

View full text Add to dashboard Cite

The all-light-atom X-ray crystal-structure analysis of cyclosporin A (l), a cyclic undecapeptide containing seven N-methylated amino acids, reveals a conformation very similar to that of the previously analysed iodo derivative which is characterised by a twisted P-pleated sheet involving the residues Me-Val-1 1, MeBmt-1, Abu-2, Sar-3, MeLeu-4, Val-5, MeLeu-6, and Ala-7. The@-bend at Sar-MeLeu-4 is of type II', and the loop of the residual amino acids involves a cis-peptide bond between MeLeu-9 and MeLeu-10. The NH proton of D-Ala-8 closes a $-bend with a H-bond to the MeLeu-6 CO group. The crystal was grown from acetone. A closely similar backbone conformation in apolar solvents such as CDCl, or C6D6 has been derived from the interpretation of the NMR spectral parameters (homo-and heteronuclear NOE effects, coupling constants, chemical-shift values of the C-, H-, and N-atoms). A minor variation in the backbone conformation between crystal and solution is observed in the region of o-Ala-8, where in solution a 3-center H-bond is established between the NH of D-Ala-8 und the carbonyl 0-atoms of both MeLeu-6 ($-turn) and o-Ala-8 (C5-bend). A recently proposed technique to identify intramolecular H-bond via heteronuclear NOE from NH proton to carbonyl C-atoms is critically analysed. The main difference between crystal and solution conformations lies in the orientation of the side chains of the unusual amino acid MeBmt kl = f60" in solution, -168" in the crystal) and of MeLeu-10 k1 = -60" in solution, +60' in the crystal). The differences in crystal and solution are caused by the break ofthe intermolecular H-bond of the OH group of MeBmt on dissolution of the crystal. The bifurcated H-bond ofo-Ala-8 twists the backbone in this region. Molecular modeling demonstrates that this is the origin of the change in the side chain conformation of MeLeu-10. The intramolecular flexibility in the crystal indicated by the thermal parameters obtained from the X-ray refinement, and in solution by an analysis of spin-lattice relaxation times in the NMR experiments, indicate a fairly rigid backbone and fixed conformations for all the side chains except for that of Abu-2 and the distal atoms of MeBmt.

show abstract

“…Such a correlation has been observed in cyclic tripeptides [42] and was in accord with force-field calculations [43]. In the case of 1 we found no correlation.…”

Section: Ala-8supporting

confidence: 91%

Peptide conformations. Part 31. The conformation of cyclosporin a in the crystal and in solution

Loosli¹,

Kessler²,

Oschkinat³

et al. 1985

Helvetica Chimica Acta

Self Cite

347

265

View full text Add to dashboard Cite

show abstract

“…Using 58 upper-distance and two dihedralangle restraints, the calculations yielded 25 out of 50 SA structures that have no NOE violations > 0.1 A, and all of which lie within 3 kcal/mol of the lowest-energy conformer (see Table 5). The two dihedral-angle restraints used restrict asp*^, to the range 30 to 90°, and P~o(NH,)~x, to between -50 and -lo", as implied by the observed 'J(a,p) coupling constants (vide supra).…”

Section: Noe's O Fmentioning

confidence: 99%

Protein‐Loop Mimetics: A Diketopiperazine‐Based Template to Stabilize Loop Conformations in Cyclic Peptides Containing the NPNA and RGD Motifs

Bisang

Weber

1996

Helvetica Chimica Acta

View full text Add to dashboard Cite

We explore here an approach to mimic the structures and biological functions of protein loops in small synthetic molecules, by grafting the loop of interest onto an organic template comprising a bicyclic diketopiperazine, prepared by the formal coupling of (2S,4S)-4-aminoproline (Pro(NH,)) and aspartic acid (Asp). The Fmoc-protected template 4 is used to prepare cycle(-Ala'-Asn2-Pro3-Asn4-Ala5-Ala6-Temp-) (5) and cyclo(-Ala'-Arg2-Gly3-Asp4-Temp-) (6) (where Temp = template derived from 4), containing the Asn-Pro-Asn-Ala (NPNA) and Arg-Gly-Asp (RGD) motifs. The conformational properties of these molecules are studied in aqueous solution by NMR and simulated-annealing methods. The NPNA motif, an immunodominant epitope on the circumsporozoite surface protein of the malaria parasite Plrrsmodium fakiparum, is shown to adopt a stable type-I 8-turn in 5.The template in 5 adopts a preferred conformation with Pro(NH,) x1 N -35O and the Asp moiety x I N 70". A different template conformation is inferred for 6, with Pro(NH,)X I N 0", but the ARGD loop appears by NMR to undergo rapid conformational averaging. Solid-phase binding assays reveal that 6 displays modest antagonist activity towards both the integrin a,& and GI& receptors.

show abstract

“…Combined 1 H NMR analysis and molecular mechanics calculations provide valuable evidence about the conformation of these systems, 1 in particular pyrrolidines, which are of great interest as subunits for natural products. 2 Previous studies on a fused pyrrolidine, namely the alkaloid physostigmine, characterized two global minima structures for the considerably constrained C-ring, the twist and envelope-twist conformations.…”

Section: Introductionmentioning

confidence: 99%

Conformational studies on indole alkaloids from Flustra foliacea by NMR and molecular modeling

Morales‐Ríos

Santos-Sánchez

Suárez‐Castillo

et al. 2002

Magnetic Reson in Chemistry

View full text Add to dashboard Cite

H and13 C NMR assignments for 1a-4a and 1b-4b were obtained using HSQC, HMBC and NOESY techniques. Differences and ambiguities from literature assignments are reconciled. For the pyrrolidine C-ring, the combined use of NMR spectroscopy and molecular mechanics calculations revealed that this ring exists in a dynamic conformational equilibrium between twist ( 2 T 1 ) and envelope-twist ( 1 E-1 T 2 ) conformations. In chloroform-d 1 , the 1 H NMR coupling constants indicate that the pyrrolidine ring is biased in favor of the envelope-twist conformation. Steric requirements of the N-prenyl group enhanced the envelope-twist ( 1 E-1 T 2 ) conformation populations.

show abstract

Peptide conformations. 20. Conformational analysis of proline rings from proton spin-spin coupling constants and force-field calculations: application to three cyclic tripeptides

Cited by 57 publications

References 2 publications

Peptide conformations. Part 31. The conformation of cyclosporin a in the crystal and in solution

Peptide conformations. Part 31. The conformation of cyclosporin a in the crystal and in solution

Protein‐Loop Mimetics: A Diketopiperazine‐Based Template to Stabilize Loop Conformations in Cyclic Peptides Containing the NPNA and RGD Motifs

Conformational studies on indole alkaloids from Flustra foliacea by NMR and molecular modeling

Contact Info

Product

Resources

About