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PCA gives an aryl aldimine and EBA an N-aryl isoquinolinium whose nitrogen is aromatic and cationic, so neither could be written while the placeholder forced a neutral single bond. Both are filled for the light and the heavy channel, leaving no probe row without a structure. The PCA imine is what a per-residue SMILES can express; the stable product closes onto the second residue's backbone amide (Suppl. Fig. 34), an isomer, so the composition is unaffected. Co-Authored-By: Claude Opus 5 <noreply@anthropic.com>
GeorgWa
requested review from
boopthesnoot,
lucas-diedrich,
mo-sameh and
mschwoer
October 14, 2026 21:56
lucas-diedrich
approved these changes
Oct 16, 2026
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- The isoDTB stereocenters are different than in the product sheet of the vendors.
- For
PCA-DTB, only the unstable intermediate product is shown - This is a Schiff-base which will likely a) hydrolyze (i.e. release the Any_N-term again) or b) continue to react to a 5-membered cyclic ring (only at N-termini). The authors observe a strong enrichment of N-terminal peptides (given the low stability of the Schiff Base). So the provided SMILES string does not correspond to the modification that is mostly observed in the spectra.
There was a bit of context missing to review the provided structures. For these specialized modifications, it would be great to get the publication link + potentially the plotted structures as context for review to reduce the number of required Google Searches + Claude Prompts
I used the following resources:
- Nature Paper describing the probes + reaction mechanism:
Zanon, P.R.A., Yu, F., Musacchio, P.Z. et al. Profiling the proteome-wide selectivity of diverse electrophiles. Nat. Chem. 17, 1712–1721 (2025). https://doi.org/10.1038/s41557-025-01902-z
- isoDTB product sheet
| PCA-DTB-heavy@K 0.0 0.0 13C(4)15N(2)C(24)H(38)N(8)O(5) 0.0 User-added 0 N([Fl])([Fl])[C@@]([H])(CCCCN=Cc%12ccc(c%11cn(CCCC[C@@H](C(N)=O)N[13C](=O)[13CH2][15NH][13C](=O)[13CH2][15NH]C(=O)CCCCC[C@H]%10NC(=O)N[C@@H]%10C)nn%11)cn%12)C(=O)[Ts] 0.0 | ||
| PCA-DTB@Any_N-term 0.0 0.0 C(28)H(38)N(10)O(5) 0.0 User-added 0 0.0 | ||
| PCA-DTB-heavy@Any_N-term 0.0 0.0 13C(4)15N(2)C(24)H(38)N(8)O(5) 0.0 User-added 0 0.0 | ||
| PCA-DTB@Any_N-term 0.0 0.0 C(28)H(38)N(10)O(5) 0.0 User-added 0 [Lv]=Cc%12ccc(c%11cn(CCCC[C@@H](C(N)=O)NC(=O)CNC(=O)CNC(=O)CCCCC[C@H]%10NC(=O)N[C@@H]%10C)nn%11)cn%12 0.0 |
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Current molecule
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- Same comment with respect to the stereochemistry of the two chiral centers as for
EBA-DTB@Any_N-term - The current smiles string encodes the initial product, a Schiff Base, which will (according to claude) rearrange during sample processing:
(Claude)
| EBA-DTB-heavy@K 0.0 0.0 13C(4)15N(2)C(28)H(41)N(7)O(6) 0.0 User-added 0 N([Fl])([Fl])[C@@]([H])(CCCC[n+]%12ccc%13ccc(OCc%11cn(CCCC[C@@H](C(N)=O)N[13C](=O)[13CH2][15NH][13C](=O)[13CH2][15NH]C(=O)CCCCC[C@H]%10NC(=O)N[C@@H]%10C)nn%11)cc%13c%12)C(=O)[Ts] 0.0 | ||
| EBA-DTB@Any_N-term 0.0 0.0 C(32)H(41)N(9)O(6) 0.0 User-added 0 0.0 | ||
| EBA-DTB-heavy@Any_N-term 0.0 0.0 13C(4)15N(2)C(28)H(41)N(7)O(6) 0.0 User-added 0 0.0 | ||
| EBA-DTB@Any_N-term 0.0 0.0 C(32)H(41)N(9)O(6) 0.0 User-added 0 [Lv+]%12C=CC%13=CC=C(OCc%11cn(CCCC[C@@H](C(N)=O)NC(=O)CNC(=O)CNC(=O)CCCCC[C@H]%10NC(=O)N[C@@H]%10C)nn%11)C=C%13C=%12 0.0 |
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Current molecule
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Structure matches the product of the reaction mechanism in this publication:
Issues
Stereoconformation at the 4-Methylimidazolidin-2-one ring seems to be different than in this structure of a vendor (see arrangement of methyl/alkyl groups at the two chiral centers)
Not saying that the vendor structure is correct though ...
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Adds new mod's which are only possible after the modification fix.