8V4B
NMR structure of a synthetic analogue of Ramoplanin A2
Summary for 8V4B
| Entry DOI | 10.2210/pdb8v4b/pdb |
| NMR Information | BMRB: 52188 |
| Descriptor | Ramoplanin A2 synthetic analogue, HEXANOIC ACID (2 entities in total) |
| Functional Keywords | antibiotic peptide, synthetic peptide, ramoplanin a2, non ribosomal peptide, arylglycine, solid phase peptide synthesis, antibiotic |
| Biological source | Actinoplanes |
| Total number of polymer chains | 1 |
| Total formula weight | 2149.31 |
| Authors | Swarbrick, J.D.,Marschall, E.A.,Cryle, M.J.,Tailhades, J. (deposition date: 2023-11-28, release date: 2025-04-16, Last modification date: 2025-04-23) |
| Primary citation | Marschall, E.,Cass, R.W.,Prasad, K.M.,Swarbrick, J.D.,McKay, A.I.,Payne, J.A.E.,Cryle, M.J.,Tailhades, J. Synthetic ramoplanin analogues are accessible by effective incorporation of arylglycines in solid-phase peptide synthesis. Chem Sci, 15:195-203, 2023 Cited by PubMed Abstract: The threat of antimicrobial resistance to antibiotics requires a continual effort to develop alternative treatments. Arylglycines (or phenylglycines) are one of the signature amino acids found in many natural peptide antibiotics, but their propensity for epimerization in solid-phase peptide synthesis (SPPS) has prevented their use in long peptide sequences. We have now identified an optimized protocol that allows the synthesis of challenging non-ribosomal peptides including precursors of the glycopeptide antibiotics and an analogue of feglymycin (1 analogue, 20%). We have exploited this protocol to synthesize analogues of the peptide antibiotic ramoplanin using native chemical ligation/desulfurization (1 analogue, 6.5%) and head-to-tail macrocyclization in excellent yield (6 analogues, 3-9%), with these compounds extensively characterized by NMR (U-shaped structure) and antimicrobial activity assays (two clinical isolates). This method significantly reduces synthesis time (6-9 days) when compared with total syntheses (2-3 months) and enables drug discovery programs to include arylglycines in structure-activity relationship studies and drug development. PubMed: 38131086DOI: 10.1039/d3sc01944f PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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