Thiostreptonyimveliso yebhaktiriya yendalo entsonkothileyo kakhulu esetyenziswa njengesihlokoi-antibiotic yezilwanyanakwaye inomsebenzi olungileyo wokulwa nemalariya kunye nomhlaza.Okwangoku, yenziwe ngokupheleleyo ngamachiza.
I-Thiostrepton, yokuqala yodwa kwiibhaktheriya kwi-1955, inomsebenzi ongaqhelekanga we-antibiotic: inqanda i-protein biosynthesis ngokuzibophelela kwi-ribosomal RNA kunye neeprotheni ezihambelana nazo.UDorothy Crowfoot Hodgkin, iBritish crystallographer kunye no-1964 owaphumelela iBhaso leNobel, wafumanisa isakhiwo ngo-1970.
I-Thiostrepton iqulethe iindandatho ze-10, iibhondi ze-peptide ze-11, i-unsaturation ebanzi, kunye ne-17 stereocenters.Owona mceli mngeni mkhulu kukuba inochuku kakhulu kwiiasidi kunye neziseko.Yikhompawundi yomzali kunye nelona lungu lintsokothileyo losapho lwe-thiopeptide lwe-antibiotic.
Ngoku le khompawundi iye yanikezela kwintetho emnandi eyenziwe ngunjingalwazi wekhemistri u-KS Nicolaou kunye noogxa bakhe beScripps Research Institute kunye neYunivesithi yaseCalifornia eSan Diego [Angew.Ikhem.amazwe ngamazwe.Abahleli, 43, 5087 kunye ne-5092 (2004)].
UChristopher J. Moody, uPhando oPhezulu kwiSebe leKhemistry kwiYunivesithi yase-Exeter, e-UK, wathi: “Oku kukudibanisa okuphawulekayo kunye nempumelelo ephawulekayo yeqela likaNicolaou.”doxorubicin D.
Isitshixo kulwakhiwo lweTHIOSTREPTONyindandatho ye-dehydropiperidine, exhasa umsila we-didehydroalanine kunye ne-macrocycles ezimbini - i-26-membered thiazoline-containing ring kunye ne-27-membered quinalcolic acid system.UNicolaou kunye noogxa bakhe benze i-ringi engundoqo ye-dehydropiperidine kwizinto ezilula zokuqalisa zisebenzisa i-biomimetic iso-Diels-Alder dimerization reaction.Eli nyathelo libalulekileyo lanceda ukuqinisekisa isindululo sika-1978 sokuba iibhaktheriya zisebenzise le ndlela yokusabela kwi-biosynthesize antibiotics ye-thiopeptide.
UNicolaou kunye noogxa bafaka i-dehydropiperidine kwi-macrocycle ene-thiazoline.Badibanisa le macrocycle kunye nesakhiwo esine-quinalcolic acid kunye ne-didehydroalanine tail precursor.Emva koko bahlambulula imveliso ukuze bafumanei-thiostrepton.
Abaphononongi bamaphepha amabini eqela bathi ukudibanisa "ngumsebenzi wobugcisa oqaqambisa itekhnoloji yezobuchwephesha kwaye ivule iihorizons ezintsha zophando olunentsingiselo kulwakhiwo, umsebenzi kunye nendlela yokwenza."
Ixesha lokuposa: Oct-31-2023