3.1. Dataset of Cyclic Peptides with Solution Structures¶
We compiled a dataset of macrocycles with available solution structures in the form of NOE distance constraints called MacroConf (Fig. 3.1). The set contains 68 compounds; of which 36 (53%) compounds are cyclic peptides made up exclusively of D&L amino acids. The remaining 32 (47%) compounds are macrocycles and contain amino acids with various chemical modifications. These 68 compounds were selected because of their available experimental NOE data. Other macrocyclic compounds with NMR data (but without NOEs) are also available but were excluded from the following analysis.
Note
The below figure is interactive. Hover over the molecule images to get more information about a specific molecule. Clicking on a molecule keeps this view open, e.g. to copy the paper reference. At the bottom (might have to scroll down slightly), the dataset can be sorted by different properties. To first see all natural cyclic peptides, one could sort by ‘is natural cyclic peptide’ in descending order.
Fig. 3.1 Overview of the MacroConf dataset showing the chemical structures of the 68 cyclic peptides and macrocycles that make up the dataset. If viewing in the interactive report, searching & sorting by various properties is possible. Additionally, clicking on a specific compound reveals further details such as the original publication, information about the NMR experiment and associated NOE data.¶
Note
The full dataset is presented in a table below (scroll to the right to see all columns), which can be displayed by clicking on ‘Click to show’. This reveals further information, such as details about the NOE experiments performed, the compound names in the original publications, etc.
| id | compound name | compound name in original paper | is natural cyclic peptide | is unnatural cyclic peptide | sequence | sequence-1 | backbone size | type of NOE available | solvent | type of NOE experiment | NMR details | NOE computation | other NMR experiments conducted | smiles | paper no | paper-link | NOE quality | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 1 | phepropeptin C | 3 | 0 | 1 | Leu-d(Phe)-Pro-Leu-d(Leu)-Ile | NaN | 6 | distance w/o errors | CDCl3, DMSO | ROESY | ROESY: 600 MHz NMR @ 25°C, mixing time of 200 ... | sufficiently resolved crosspeaks were integrat... | J-couplings were gathered from the 1H Chlorofo... | CCC(C)[C@@H]3NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](C... | 1 | http://dx.doi.org/10.1021/acsmedchemlett.6b00100 | 0 |
| 1 | 2 | - | 6R | 0 | 0 | Beta H Phe, Phe, R-Pro, R-Asu, (DMSO). In H2O:... | NaN | 4 (but 13 atoms instead of 12 b/c of beta a.a.) | upper limit only (bins) | DMSO; 90% H2O 10% CD3CN | ROESY | 400 ms ROESY spectra. ~ 4 μmol peptide in 500 ... | ROE cross-peak volumes were classified by visu... | J couplings provided. Backbone dihedral angle ... | COC(=O)CCCCC[C@H]4NC(=O)[C@H]1CCCN1C(=O)[C@H](... | 2 | 10.1021/ja029205t | 0 |
| 2 | 3 | - | 6S | 0 | 0 | Beta Phe, Phe, R-Pro, S-Asu | NaN | 5 (but 13 atoms instead of 12 b/c of beta a.a.) | upper limit only (bins) | DMSO | ROESY | 400 ms ROESY spectra. ~ 4 μmol peptide in 500 ... | ROE cross-peak volumes were classified by visu... | J couplings provided. Backbone dihedral angle ... | COC(=O)CCCCC[C@@H]4NC(=O)[C@H]1CCCN1C(=O)[C@H]... | 2 | 10.1021/ja029205t | 0 |
| 3 | 4 | - | 3 | 0 | 0 | - | NaN | 4 | no distance, but upper/lower bound | DMSO | ROESY | The ROESY experiments were performed with mixi... | Distance restraints were calculated from the v... | J couplings and dihedrals provided. | CSCCC4NC(=O)C(CC(C)C)NC(=O)C[C@@H]([C@H]2O[C@@... | 3 | http://dx.doi.org/10.1021/jo2019834 | 0 |
| 4 | 5 | - | 4 | 0 | 0 | - | NaN | 4 | no distance, but upper/lower bound | DMSO | ROESY | The ROESY experiments were performed with mixi... | Distance restraints were calculated from the v... | J couplings and dihedrals provided. VT study o... | CSCCC5NC(=O)C[C@@H]([C@H]2O[C@@H]1OC(C)(C)O[C@... | 3 | http://dx.doi.org/10.1021/jo2019834 | 0 |
| 5 | 6 | - | 5 | 0 | 0 | - | NaN | 4 | no distance, but upper/lower bound | DMSO | ROESY | The ROESY experiments were performed with mixi... | Distance restraints were calculated from the v... | J couplings and dihedrals provided. | CSCCC5NC(=O)C(Cc1ccccc1)NC(=O)C[C@@H]([C@H]3O[... | 3 | http://dx.doi.org/10.1021/jo2019834 | 0 |
| 6 | 7 | - | 6 | 0 | 0 | - | NaN | 4 | no distance, but upper/lower bound | DMSO | ROESY | The ROESY experiments were performed with mixi... | Distance restraints were calculated from the v... | J couplings and dihedrals provided. VT study o... | CSCCC6NC(=O)C(Cc1ccccc1)NC(=O)C(Cc2ccccc2)NC(=... | 3 | http://dx.doi.org/10.1021/jo2019834 | 0 |
| 7 | 8 | - | 7 | 0 | 0 | - | NaN | 4 | no distance, but upper/lower bound | DMSO | ROESY | The ROESY experiments were performed with mixi... | Distance restraints were calculated from the v... | J couplings and dihedrals provided. VT study o... | CSCCC5NC(=O)C(Cc1ccccc1)NC(=O)C(CC(C)C)NC(=O)C... | 3 | http://dx.doi.org/10.1021/jo2019834 | 0 |
| 8 | 9 | - | 8 | 0 | 0 | - | NaN | 4 | no distance, but upper/lower bound | DMSO | ROESY | The ROESY experiments were performed with mixi... | Distance restraints were calculated from the v... | J couplings and dihedrals provided. VT study o... | CSCCC6NC(=O)C(Cc1ccccc1)NC(=O)C(Cc2ccccc2)NC(=... | 3 | http://dx.doi.org/10.1021/jo2019834 | 0 |
| 9 | 10 | - | 2 | 0 | 0 | c-(Trp_eps-Ile_eps-D-Ala_Aoda) | NaN | 4 | upper limit only (bins) | DMSO | ROESY | ~7–9 mM solution of peptide in DMSO-d6 on a Br... | Integration was performed using the program NE... | - | CCC(=O)CCCCC[C@@H]4NC(=O)[C@@H](C)n1cc(nn1)[C@... | 4 | 10.1002/anie.200805900 | 0 |
| 10 | 11 | - | 11 | 0 | 0 | c-(Trp_eps-Leu_eps-D-Ala_Aoda) | NaN | 4 | upper limit only (bins) | DMSO | ROESY | ~7–9 mM solution of peptide in DMSO-d6 on a Br... | Integration was performed using the program NE... | - | CCC(=O)CCCCC[C@@H]4NC(=O)[C@@H](C)n1nncc1[C@H]... | 4 | 10.1002/anie.200805900 | 0 |
| 11 | 12 | - | 12 | 0 | 0 | c-(Trp_eps-D-Leu_eps-D-Ala_Aoda) | NaN | 4 | upper limit only (bins) | DMSO | ROESY | ~7–9 mM solution of peptide in DMSO-d6 on a Br... | Integration was performed using the program NE... | - | CCC(=O)CCCCC[C@@H]4NC(=O)[C@@H](C)n1nncc1[C@@H... | 4 | 10.1002/anie.200805900 | 0 |
| 12 | 13 | - | 4a | 0 | 0 | c(GQSAGD-PVhS(Me)AN) | NaN | 10 | distance w/o errors | DMSO | NOESY | 900 MHz, 25C, | NOE build-ups were recorded without solvent su... | VT-NMR, Amide proton temperature coefficients,... | COCC[C@@H]2NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)N... | 5 | http://pubs.acs.org/doi/abs/10.1021/acs.bioche... | 5 |
| 13 | 14 | - | 4b | 0 | 0 | c(GQXAGD-PVhS(Me)AN) | NaN | 10 | distance w/o errors | DMSO | NOESY | 900 MHz, 25C, | NOE build-ups were recorded without solvent su... | VT-NMR, Amide proton temperature coefficients,... | CC[C@@H]2NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H]1CCCN... | 5 | http://pubs.acs.org/doi/abs/10.1021/acs.bioche... | 5 |
| 14 | 15 | - | 5 | 0 | 0 | c(NVA(Cl)AGD-PVS(Me) QG) | NaN | 10 | distance w/o errors | DMSO | NOESY | 900 MHz, 25C, | NOE build-ups were recorded without solvent su... | VT-NMR, Amide proton temperature coefficients,... | COC[C@@H]2NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C... | 5 | http://pubs.acs.org/doi/abs/10.1021/acs.bioche... | 5 |
| 15 | 16 | - | 1 | 0 | 0 | Cyclo-[Tyr(N-Me)-D-Leu(N-Me)-Leu-Leu(N-Me)-D-L... | NaN | 6 | upper limit only (bins) | CDCl3, DMSO | ROESY | 600 MHz, ROESY mixing time of 350ms. 298 K | 52 ROEs CDCl3, 57 ROEs DMSO. ROE cross-peak vo... | HD exchange (CDCl3 298K, DMSO 298K); variable ... | CC(C)C[C@@H]2NC(=O)[C@H](Cc1ccc(O)cc1)N(C)C(=O... | 6 | 10.1002/cbic.201500441 | 0 |
| 16 | 17 | - | 2 | 0 | 0 | Cyclo-[Tyr(N-Me)-D-Pro-Leu-Leu(N-Me)-D-Leu(N-M... | NaN | 6 | upper limit only (bins) | CDCl3, DMSO | ROESY | 600 MHz, ROESY mixing time of 350ms. 298 K | 19 ROEs CDCl3, 18 ROEs DMSO. ROE cross-peak vo... | HD exchange (CDCl3 298K, DMSO 298K); variable ... | CC(C)C[C@@H]3NC(=O)[C@H](Cc1ccc(O)cc1)N(C)C(=O... | 6 | 10.1002/cbic.201500441 | 0 |
| 17 | 18 | - | 3 | 0 | 0 | Cyclo-[Tyr(N-Me)-D-Pro-Leu-Leu(N-Me)-D-Pro-Leu] | NaN | 6 | upper limit only (bins) | CDCl3, DMSO | ROESY | 600 MHz, ROESY mixing time of 350ms. 298 K | 39 ROEs CDCl3, 46 ROEs DMSO. ROE cross-peak vo... | HD exchange (CDCl3 298K, DMSO 298K); variable ... | CC(C)C[C@@H]4NC(=O)[C@H](Cc1ccc(O)cc1)N(C)C(=O... | 6 | 10.1002/cbic.201500441 | 0 |
| 18 | 19 | - | 1 | 0 | 0 | cyclo[PGLGF]odz/ethyl | NaN | 5 | no distance, but upper/lower bound | DMSO | ROESY | 500 MHz, ROESY mixing time: 150 ms | Integrated volumes of ROE crosspeaks were conv... | VT NMR, NH-CaH 3J coupling constants | CC[C@H]4c1nnc(o1)[C@H](Cc2ccccc2)NC(=O)CNC(=O)... | 7 | http://dx.doi.org/10.1038/nchem.2636 | 0 |
| 19 | 20 | - | 24 | 0 | 0 | cyclo[PSLYG]odz/benzyl | NaN | 5 | no distance, but upper/lower bound | DMSO | ROESY | 500 MHz, ROESY mixing time: 150 ms | Integrated volumes of ROE crosspeaks were conv... | VT NMR, NH-CaH 3J coupling constants | CC(C)C[C@@H]4NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1... | 7 | http://dx.doi.org/10.1038/nchem.2636 | 0 |
| 20 | 21 | - | 1 | 0 | 0 | cyclo-(-Val-b-Hala-Phe-Leu-Ile-) | NaN | 5 | distance and upper bound | TFE | NOESY | mixing times between 320 and 440 ms in 40 ms s... | The acquired data was processed with Xwin-NMR ... | VT NMR, 3J HN-Ha as validation | [H][C@](C(C)C)(C(N[C@@](C)(C1)[H])=O)NC([C@]([... | 8 | 10.1002/bip.20859 | 5 |
| 21 | 22 | - | 2 | 1 | 0 | cyclo-(-Ser-Pro-Leu-Asn-Asp-) | SPLND | 5 | distance and upper bound | DMSO | NOESY | mixing times between 320 and 440 ms in 50 ms s... | The acquired data was processed with Xwin-NMR ... | VT NMR, 3J HN-Ha as validation | N2[C@@]([H])(CO)C(=O)N1[C@@]([H])(CCC1)C(=O)N[... | 8 | 10.1002/bip.20859 | 5 |
| 22 | 23 | - | 3 | 0 | 0 | cyclo-(-Ser-Pro-Leu-b-Hasn-Asp-) | NaN | 5 | distance and upper bound | DMSO | NOESY | mixing times between 320 and 440 ms in 40 ms s... | The acquired data was processed with Xwin-NMR ... | VT NMR, 3J HN-Ha as validation | [H][C@](CO)(C(N1[C@@](CCC1)(C(N[C@@](CC(C)C)(C... | 8 | 10.1002/bip.20859 | 5 |
| 23 | 24 | - | 4a, 4b | 1 | 0 | cyclo-(-Ser-Pro-Leu-Asn-Val-Asp-) | NaN | 6 | distance and upper bound | DMSO | NOESY | mixing times between 320 and 440 ms in 20 ms s... | The acquired data was processed with Xwin-NMR ... | VT NMR, 3J HN-Ha as validation | N2[C@@]([H])(CO)C(=O)N1[C@@]([H])(CCC1)C(=O)N[... | 8 | 10.1002/bip.20859 | 5 |
| 24 | 25 | - | 5 | 0 | 0 | cyclo-(-Ser-b-Hpro-Leu-Asn-Ile-Asp-) | NaN | 5 | distance and upper bound | DMSO | NOESY | mixing times between 320 and 440 ms in 40 ms s... | The acquired data was processed with Xwin-NMR ... | VT NMR, 3J HN-Ha as validation | [H][C@](CO)(C(N1[C@]2(CCC1)[H])=O)NC([C@]([H])... | 8 | 10.1002/bip.20859 | 5 |
| 25 | 26 | - | 6 | 0 | 0 | cyclo-(-b-Hser-Pro-Leu-b-Hasn-Ile-Asp-) | NaN | 5 | distance and upper bound | DMSO | NOESY | mixing times between 320 and 440 ms in 40 ms s... | The acquired data was processed with Xwin-NMR ... | VT NMR, 3J HN-Ha as validation | [H][C@](CO)(CC(N1[C@@](CCC1)(C(N[C@@](CC(C)C)(... | 8 | 10.1002/bip.20859 | 5 |
| 26 | 27 | - | RI1 | 0 | 1 | cyclo(-VfdGr-) | NaN | 5 | distance w errors | DMSO | NOESY | The NOE effects were quantified by NOESY exper... | The intensities of\ncross peaks were measured ... | J coupling constants, Temperature dependence | N2[C@@]([H])(C(C)C)C(=O)N[C@]([H])(Cc1ccccc1)C... | 9 | https://doi.org/10.1021/ja961908l | 0 |
| 27 | 28 | - | RI2 | 0 | 1 | cyclo(-vFdGr-) | NaN | 5 | distance w errors | DMSO | NOESY | The NOE effects were quantified by NOESY exper... | The intensities of\ncross peaks were measured ... | J coupling constants, Temperature dependence | N2[C@]([H])(C(C)C)C(=O)N[C@@]([H])(Cc1ccccc1)C... | 9 | https://doi.org/10.1021/ja961908l | 0 |
| 28 | 29 | - | RI3 | 0 | 1 | cyclo(-vfDGr-) | NaN | 5 | distance w errors | DMSO | NOESY | The NOE effects were quantified by NOESY exper... | The intensities of\ncross peaks were measured ... | J coupling constants, Temperature dependence | N2[C@]([H])(C(C)C)C(=O)N[C@]([H])(Cc1ccccc1)C(... | 9 | https://doi.org/10.1021/ja961908l | 0 |
| 29 | 30 | - | RI4 | 0 | 1 | cyclo(-vfdGR-) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | The NOE effects were quantified by NOESY exper... | The intensities of\ncross peaks were measured ... | J coupling constants, Temperature dependence | N2[C@]([H])(C(C)C)C(=O)N[C@]([H])(Cc1ccccc1)C(... | 9 | https://doi.org/10.1021/ja961908l | 0 |
| 30 | 31 | - | RI5 | 0 | 1 | cyclo(-vfdGr-) | NaN | 5 | distance w errors | DMSO | NOESY | The NOE effects were quantified by NOESY exper... | The intensities of\ncross peaks were measured ... | J coupling constants, Temperature dependence | N2[C@]([H])(C(C)C)C(=O)N[C@]([H])(Cc1ccccc1)C(... | 9 | https://doi.org/10.1021/ja961908l | 0 |
| 31 | 32 | - | P3 | 0 | 1 | cyclo(-RGdFV-) | NaN | 5 | distance w errors | DMSO | NOESY | The NOE effects were quantified by NOESY exper... | The intensities of\ncross peaks were measured ... | J coupling constants, Temperature dependence | N2[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@]([H])... | 9 | https://doi.org/10.1021/ja961908l | 0 |
| 32 | 33 | - | P5 | 1 | 0 | cyclo(-RGDFV-) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | The NOE effects were quantified by NOESY exper... | The intensities of\ncross peaks were measured ... | J coupling constants | N2[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 9 | https://doi.org/10.1021/ja961908l | 0 |
| 33 | 34 | - | 1 | 0 | 0 | c(-Arg1-Gly2-Asp3-D-PheV[CH2-NH]Val5-) (1) | NaN | 5 | no distance, but upper/lower bound | DMSO H2O mixture | NOESY | 175-ms mixing time. Two NOESY spectra were rec... | NOEs were obtained by integration of cross pea... | J coupling constants, Temperature dependence | [H][C@@](CCCNC(N)=N)(C(NCC(N[C@](CC(O)=O)(C(N[... | 10 | https://doi.org/10.1021/ja00096a034 | 0 |
| 34 | 35 | - | P2 | 0 | 1 | c(RGDkV) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | N1[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 35 | 36 | - | P3 | 0 | 1 | c(RGDpV) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | N2[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 36 | 37 | - | P5 | 0 | 0 | c(RGDticV): 1,2,3,4-tetrahydroisochinoline ca... | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | [H][C@](CCCNC(N)=N)(C(NCC(N[C@@](CC(O)=O)(C(N1... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 37 | 38 | - | P6 | 0 | 1 | c(RGDwV) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | N3[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 38 | 39 | - | P8 | 0 | 1 | c(RGDfK) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | N2[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 39 | 40 | - | P15 | 0 | 1 | c(RGDKv) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | N1[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 40 | 41 | - | P18 | 0 | 1 | c(RGDWv) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | N3[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 41 | 42 | - | P20 | 0 | 1 | c(RGDFk) | NaN | 5 | distance w errors | DMSO | NOESY, ROESY | AMX 500 spectrometer. 30 - 40 mM solutions of ... | Quantitative information on interproton distan... | J couplings, temperature gradients | N2[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 11 | https://doi.org/10.1021/ja9603721 | 0 |
| 42 | 43 | - | PA1 | 0 | 0 | c(RGD"S-ANC") | NaN | 4 | distance w errors | DMSO | NOESY | mixing time NOESY: 150 ms. 20 mM solutions | the volume integrals of the crosspeaks were me... | J coupling constants, Temperature dependence | [H][C@](CCCNC(N)=N)(C(NCC(N[C@@](CC(O)=O)(C(N[... | 12 | https://doi.org/10.1021/ja9608757 | 0 |
| 43 | 44 | - | PA2 | 0 | 0 | c(RGD"R-ANC") | NaN | 4 | distance w errors | DMSO | ROESY | compensated ROESY with 200 ms mixing time. 20 ... | the volume integrals of the crosspeaks were me... | J coupling constants, Temperature dependence | [H][C@](CCCNC(N)=N)(C(NCC(N[C@@](CC(O)=O)(C(N[... | 12 | https://doi.org/10.1021/ja9608757 | 0 |
| 44 | 45 | - | PA3 | 0 | 0 | c(RGD"BTD") | NaN | 4 | distance w errors | DMSO | NOESY | mixing time NOESY: 150 ms. 20 mM solutions | the volume integrals of the crosspeaks were me... | J coupling constants, Temperature dependence | [H][C@](CCCNC(N)=N)(C(NCC(N[C@@](CC(O)=O)(C(N[... | 12 | https://doi.org/10.1021/ja9608757 | 0 |
| 45 | 46 | - | PA4 | 0 | 0 | c(RGD"Spiro") | NaN | 4 | distance w errors | DMSO | ROESY | compensated ROESY with 200 ms mixing time. 20 ... | the volume integrals of the crosspeaks were me... | J coupling constants, Temperature dependence | [H][C@](CCCNC(N)=N)(C(NCC(N[C@@](CC(O)=O)(C(N1... | 12 | https://doi.org/10.1021/ja9608757 | 0 |
| 46 | 47 | - | PA5 | 0 | 0 | c(RGD"BTD"V) | NaN | 4 | distance w errors | DMSO | ROESY | compensated ROESY with 200 ms mixing time. 20 ... | the volume integrals of the crosspeaks were me... | J coupling constants, Temperature dependence | [H][C@](CCCNC(N)=N)(C(NCC(N[C@@](CC(O)=O)(C(N[... | 12 | https://doi.org/10.1021/ja9608757 | 0 |
| 47 | 48 | - | PA6 | 0 | 0 | c(RaD"BTD"V) | NaN | 4 | distance w errors | DMSO | ROESY | compensated ROESY with 200 ms mixing time. 20 ... | the volume integrals of the crosspeaks were me... | J coupling constants, Temperature dependence | [H][C@](CCCNC(N)=N)(C(N[C@](C)(C(N[C@@](CC(O)=... | 12 | https://doi.org/10.1021/ja9608757 | 0 |
| 48 | 49 | - | - | 1 | 0 | c(RGDFPG) trans / c(RGDFPG) cis | NaN | 6 | distance w errors | DMSO | NOESY, ROESY | 10-20 mM peptide concentration | The ROES and NOES were translated into interpr... | J coupling constants, Temperature dependence | N2[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 13 | https://doi.org/10.1002/prot.340150303 | 0 |
| 49 | 50 | - | - | 1 | 0 | c(RGDFPA) trans / c(RGDFPA)cis | NaN | 6 | distance w errors | DMSO | NOESY, ROESY | 10-20 mM peptide concentration | The ROES and NOES were translated into interpr... | J coupling constants, Temperature dependence | N2[C@@]([H])(CCCNC(=N)N)C(=O)NCC(=O)N[C@@]([H]... | 13 | https://doi.org/10.1002/prot.340150303 | 0 |
| 50 | 51 | - | - | 1 | 0 | cyclo[-D-Pro-Ala2-Ala3-Ala4-Ala5-] | pAAAA | 5 | no distance, but upper/lower bound | DMSO | NOESY | - | The distance restraints were obtained using th... | NaN | N21[C@]([H])(CCC1)C(=O)N[C@@]([H])(C)C(=O)N[C@... | 14 | https://doi.org/10.1021/ja00082a027 | 0 |
| 51 | 52 | - | 1 | 0 | 1 | cyclo-(Pro-Ser-leu-Asp-Val) | PSlDV | 5 | distance w errors | aqueous solution | ROESY | ROESY spectra were acquired with mixing times ... | For Calculation of the NOE distance restraints... | J couplings | N21[C@@]([H])(CCC1)C(=O)N[C@@]([H])(CO)C(=O)N[... | 15 | http://dx.doi.org/10.1021/acs.jcim.8b00097 | 5 |
| 52 | 53 | cilengitide | 2 | 0 | 0 | cilengitide cyclo-(Arg-Gly-Asp-phe-([N-Me]Val)) | NaN | 5 | distance and upper bound | aqueous solution, DMSO, MeOH, CDCl3 | ROESY | ROESY: 600 MHz. 150 ms mixing time | ROE cross peaks in corresponding ROESY spectra... | J coupling constants, , VT studies | O=C1N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](C(=... | 15 | http://dx.doi.org/10.1021/acs.jcim.8b00097 | 0 |
| 53 | 54 | - | 3 | 1 | 0 | cyclo-(Arg-Arg-Trp-Trp-Arg-Phe) | NaN | 6 | no distance, but upper/lower bound | aqueous solution | NOESY, ROESY | NOESY (mixing time 80 ms), and ROESY (80 ms mi... | NOESY cross peaks were fitted with a Gaussian ... | J coupling constants | N3[C@@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(CCCNC... | 15 | http://dx.doi.org/10.1021/acs.jcim.8b00097 | 0 |
| 54 | 55 | - | - | 1 | 0 | cyclo [Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly] | NaN | 10 | no distance, but upper/lower bound | aqueous solution | NOESY, ROESY | The temperature was 5 °C for the buildup serie... | All NOEs were negative (i.e., diagonal and cro... | NaN | N3[C@@]([H])(CO)C(=O)N[C@@]([H])(Cc1ccc(O)cc1)... | 16 | https://doi.org/10.1007/bf00355044 | 5 |
| 55 | 56 | - | - | 1 | 0 | c(C-L-L-R-M-R-S-I-C) disulfide-linked | NaN | 9 | distance w errors | aqueous solution | NOESY, ROESY | NMR spectra were obtained at 279.0 K\nfrom pep... | Nuclear Overhauser effect cross-peaks were ass... | J couplings, VT experiment | N[C@@]([H])(CS1)C(=O)N[C@@]([H])(CC(C)C)C(=O)N... | 17 | https://doi.org/10.1034/j.1399-3011.2003.00070.x | 5 |
| 56 | 57 | 6BE9 | 7.1 | 0 | 1 | T(DLY)NDT(DSG)(DPR) | TkNDTnp | 7 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@@]([H])([C@]([H])(O)C)C(=O)N[C@]([H])(CCC... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 57 | 58 | 6BEW | 7.2 | 0 | 1 | (DHI)P(DAS)(DGN)(DSN)(DGL)P | hPdqseP | 7 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@]([H])(CC1=CN=C-N1)C(=O)N1[C@@]([H])(CCC1... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 58 | 59 | 6BE7 | 8.1 | 0 | 1 | DDPT(DPR)(DAR)Q(DGN) | DDPTprQq | 8 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@@]([H])(CC(=O)O)C(=O)N[C@@]([H])(CC(=O)O)... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 59 | 60 | 6BEN | 8.2 | 0 | 1 | (DAR)Q(DPR)(DGN)R(DGL)PQ | rQpqRePQ | 8 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@]([H])(CCCNC(=N)N)C(=O)N[C@@]([H])(CCC(=O... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 60 | 61 | 6BEO | 9.1 | 0 | 1 | (DPR)PY(DHI)PKDL(DGN) | pPYhPKDLq | 9 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N21[C@]([H])(CCC1)C(=O)N1[C@@]([H])(CCC1)C(=O)... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 61 | 62 | 6BER | 10.2 | 0 | 1 | E(DVA)DP(DGL)(DHI)(DPR)N(DAL)(DPR) | EvDPehpNap | 10 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@@]([H])(CCC(=O)O)C(=O)N[C@]([H])(C(C)C)C(... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 62 | 63 | 6BF3 | 7.3a | 0 | 1 | QDP(DPR)K(2TL)(DAS) | QDPpK(2TL)d | 7 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | [H][C@](CCC(N)=O)(C(N[C@@](CC(O)=O)(C(N1[C@@](... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 63 | 64 | 6BEQ | 10.1 | 0 | 1 | AAR(DVA)(DPR)R(DLE)(DTH)PE | AARvpRltPE | 10 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@@]([H])(C)C(=O)N[C@@]([H])(C)C(=O)N[C@@](... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 64 | 65 | 6BET | 12_ss | 0 | 1 | H(DPR)(DVA)CIP(DPR)E(DLY)VC(DGL) | HpvCIPpEkVCe | 12 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@@]([H])(CC1=CN=C-N1)C(=O)N1[C@]([H])(CCC1... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 65 | 66 | 6BF5 | 7.3a | 0 | 1 | QDP(DPR)K(DTH)(DAS) | QDPpKtd | 7 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@@]([H])(CCC(=O)N)C(=O)N[C@@]([H])(CC(=O)O... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 66 | 67 | 6BEU | 14_ss | 0 | 1 | (DCY)N(DVA)(DPR)DVYC(DPR)(DSG)KY(DVA)(DPR) | cNvpDVYCpnKYvp | 14 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@]([H])(CS)C(=O)N[C@@]([H])(CC(=O)N)C(=O)N... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
| 67 | 68 | 6BES | 11_ss | 0 | 1 | (DAL)Q(DPR)(DCY)(DLY)DS(DTY)(DCY)P(DSN) | aQpckDSycPs | 11 | NOE constraints, 20 lowest conformers | aqueous solution | NOESY, ROESY | NMR data obtained at 5C, 25C. 5C for 2D-ROESY ... | Distance restraints were derived from NOE inte... | hydrogen-bonding restraints were inferred from... | N2[C@]([H])(C)C(=O)N[C@@]([H])(CCC(=O)N)C(=O)N... | 18 | https://doi.org/10.1126/science.aap7577 | 5 |
All 68 macrocycles have associated experimental NOE data of various quality. 24 compounds (35%) have high-quality NOE data, NOE data that is based on NMR measurements (NOESY, ROESY) with multiple mixing times. The dataset was compiled by hand, but to use the associated NOE data in the subsequent analysis steps, we developed a semi-automatic workflow shown schematically in Fig. 3.2. This workflow translates the printed table of NOEs found in literature into a csv-based representation that can be utilised later within our analysis.
Fig. 3.2 Semi-automatic workflow to extract molecular structures and associated NOE data from publications. The topology parametrisation process for natural cyclic peptides is also shown.¶
For natural cyclic peptides, the SMILES string was derived from the amino acid sequence via the python toolkit Peplibgen.[53] For macrocyclic compounds the OSRA software[54] was used to extract the molecular structure from images found in corresponding publications. Any errors and inaccuracies of this software were fixed by hand. The resulting SMILES strings were then used to define a molecular topology via a multi-step process. First, the SMILES string was converted into a 3D PDB file via OpenBabel[55] (which adds appropriate atom types). Then, the .pdb file was cleaned with pdb4amber and parametrised with tleap. Using tleap we produced a range of different output file formats (amber topology file, pdb file, …). These steps are only valid for natural cyclic peptides and may need slight alterations for macrocycles depending on forcefields used. NOE tables printed in papers were extracted from the pdf-file via tabula[56]. A custom-made Python script queried the user to match all atom names provided in the paper with the atom numbers of the molecular topology. To facilitate this, the molecular topology file was visualized as a 2D structure annotated with atom numbers via RDKit[57]. This process results in a computer readable NOE representation that matches the molecular topology of the macrocycles.