6MW2

cyclo-Mle-Phe-Mle-D-Phe. D-Phe analogue of pseudoxylallemycin A.

6MW2 の概要

• エントリーDOI: 10.2210/pdb6mw2/pdb
• 関連するPDBエントリー: 6MVZ 6MW0 6MW1
• 関連するBIRD辞書のPRD_ID: PRD_002368
• 分子名称: pseudoxylallemycin A (1 entity in total)
• 機能のキーワード: tetrapeptide, cyclic peptide, n-methyl leucine, analogue of pseudoxylallemycin a, antibiotic
• 由来する生物種: Xylaria
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 566.73

構造登録者

Cameron, A.J.,Harris, P.W.R.,Brimble, M.A.,Squire, C.J. (登録日: 2018-10-29, 公開日: 2019-09-11, 最終更新日: 2024-10-23)

主引用文献

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

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: 30941386
DOI: 10.1039/c9ob00227h

実験手法

X-RAY DIFFRACTION (0.77 Å)