6MW2
cyclo-Mle-Phe-Mle-D-Phe. D-Phe analogue of pseudoxylallemycin A.
Summary for 6MW2
| Entry DOI | 10.2210/pdb6mw2/pdb |
| Related | 6MVZ 6MW0 6MW1 |
| Related PRD ID | PRD_002368 |
| Descriptor | pseudoxylallemycin A (1 entity in total) |
| Functional Keywords | tetrapeptide, cyclic peptide, n-methyl leucine, analogue of pseudoxylallemycin a, antibiotic |
| Biological source | Xylaria |
| Total number of polymer chains | 1 |
| Total formula weight | 566.73 |
| Authors | Cameron, A.J.,Harris, P.W.R.,Brimble, M.A.,Squire, C.J. (deposition date: 2018-10-29, release date: 2019-09-11, Last modification date: 2024-10-23) |
| Primary citation | Cameron, A.J.,Squire, C.J.,Gerenton, A.,Stubbing, L.A.,Harris, P.W.R.,Brimble, M.A. Investigations of the key macrolactamisation step in the synthesis of cyclic tetrapeptide pseudoxylallemycin A. Org.Biomol.Chem., 17:3902-3913, 2019 Cited by PubMed Abstract: The total synthesis and structural confirmation of naturally occurring all l-cyclic tetrapeptide pseudoxylallemycin A is reported. X-ray crystallography revealed that the linear precursor adopted an all-trans (ttt) extended linear conformation, while its cyclic derivative adopts a trans,cis,trans,cis (tctc) conformation. Two kinetically favoured cyclic conformers prone to hydrolysis initially formed rapidly during cyclisation, with subsequent conversion to the thermodynamically stable tctc macrocycle taking place slowly. We postulate the initial unstable cyclic product undergoes an unprecedented nucleophilic ring opening with either the T3P or PyAOP by-products to give the linear ttt structure as a reactivated species and through a series of equilibria is slowly consumed by cyclisation to the thermodynamic product pseudoxylallemycin A. Consumption of the reactivated species by formation of pseudoxylallemycin A requires a trans-cis isomerism to occur and necessitates moderately increased reaction temperatures. Cyclisation with T3P was found to provide the greatest stereoretention. Synthesis and X-ray crystallography of the C-terminal epimer demonstrated its cyclisation to be kinetically favoured and to proceed without epimerisation despite also bearing an all-trans backbone. PubMed: 30941386DOI: 10.1039/c9ob00227h PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (0.77 Å) |
Structure validation
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