Total synthesis of thiangazole, a novel naturally occurring HIV-1 inhibitor from Polyangium sp

Boyce, Richard J.; Mulqueen, G. C.; Pattenden, Gerald

doi:10.1016/0040-4020(95)00356-d

Cited by 58 publications

(12 citation statements)

References 20 publications

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“…as the key fragment in numerous medicinal molecules such as curacin A, [4] thiangazole, [5] deflazacor, [6] and 2-indolyloxazoline. [7] Additionally, enantiomerically pure 2-thiazolines and 2-oxazolines are also extensively used as chiral auxiliaries or chiral ligands in organic synthesis.…”

Section: Introductionmentioning

confidence: 99%

Solvent‐Free Tandem Synthesis of 2‐Thiazolines and 2‐Oxazolines Catalyzed by a Copper Catalyst

Baoyue

Zhang

et al. 2012

Eur J Org Chem

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Section: Introductionmentioning

confidence: 99%

Solvent‐Free Tandem Synthesis of 2‐Thiazolines and 2‐Oxazolines Catalyzed by a Copper Catalyst

Baoyue

Zhang

et al. 2012

Eur J Org Chem

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“…Derivative 2 was constructed on 2-chlorochlorotrityl resin using standard Fmoc-synthesis conditions. NFmoc-cinnamic acid (21) and 3-(t-butoxycarbonylthio)propanioc acid (22) were then coupled to install the requisite thiol tail. Finally, resin cleavage and thiol deprotection led to thiol derivative 2 in good yield.…”

Section: Resultsmentioning

confidence: 99%

“…Fmoc-Ile-OH, Fmoc-cinnaminic acid (21) and 3-(t-butoxycarbonylthio)propanioc acid (22) were sequentially coupled on using standard Fmoc synthesis conditions using HCTU (3 eq) and diisopropylethylamine (8 eq). The negative control, 3, was constructed in a similar manner as 2 with 2-chlorotrityl resin loaded with Fmoc-Gly-OH, Fmoc -7-aminoheptanoic acid and 3-(t-butoxycarbonylthio) propanioc acid.…”

Section: Methods (A Detailed Version Is Provided As Supporting Informmentioning

confidence: 99%

Gold nanoparticles as a platform for creating a multivalent poly-SUMO chain inhibitor that also augments ionizing radiation

Perkins

Shen

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Protein-protein interactions mediated by ubiquitin-like (Ubl) modifications occur as mono-Ubl or poly-Ubl chains. Proteins that regulate poly-SUMO (small ubiquitin-like modifier) chain conjugates play important roles in cellular response to DNA damage, such as those caused by cancer radiation therapy. Additionally, high atomic number metals, such as gold, preferentially absorb much more X-ray energy than soft tissues, and thus augment the effect of ionizing radiation when delivered to cells. In this study, we demonstrate that conjugation of a weak SUMO-2∕3 ligand to gold nanoparticles facilitated selective multivalent interactions with poly-SUMO-2∕3 chains leading to efficient inhibition of poly-SUMOchain-mediated protein-protein interactions. The ligand-gold particle conjugate significantly sensitized cancer cells to radiation but was not toxic to normal cells. This study demonstrates a viable approach for selective targeting of poly-Ubl chains through multivalent interactions created by nanoparticles that can be chosen based on their properties, such as abilities to augment radiation effects.polyubiquitin chain | radiation sensitization | SUMO-binding motif (SBM) | SUMO-interacting motif (SIM) P rotein-protein interactions mediated by mono-Ubl (ubiquitinlike proteins) or poly-Ubl modifications are among the most important signaling and regulatory mechanisms that control nearly every aspect of cellular functions (1). It has been well established that the small ubiquitin-like modifiers (SUMO), SUMO-1, SUMO-2, and SUMO-3, play essential roles in cellular response to DNA damage (2). SUMO-2 and -3 are nearly identical, but share less than 50% sequence homology to SUMO-1 (3, 4). SUMO-2 and 3 are distinct from SUMO-1 in that they carry internal SUMO modification sites at their N-termini to form poly-SUMO chains (5).In most cases, a Ubl serves as a platform for interactions with other proteins. For instance, ubiquitylation dependent processes are mediated by ubiquitin-binding motifs in receptor proteins, such as the proteosome (6). SUMO-dependent functions are mediated by a SUMO-interaction motif (SIM; also known as a SUMO-binding motif, SBM) (7, 8) that serves as receptor of SUMO modified proteins. Recent studies have shown that a SUMO-targeted ubiquitin ligase (STUBL) is important in DNA damage response, and the ligase specifically recognizes poly-SUMO-2∕3 chains to ubiquitinate poly-SUMO modified proteins for degradation (9)(10)(11)(12)(13)(14). These studies suggest that inhibiting poly-SUMO-2∕3 interactions with down-stream effectors, such as STUBL, can inhibit DNA damage response. However, an effective approach to disrupting poly-Ubl chain-mediated cellular functions is lacking. In addition to proteosome inhibitors, a small molecule was identified that binds to and alters the conformation of polyubiquitin chains such that their interactions with the proteosome are inhibited (15). However, the negative charge of this small molecule prevents its translocation into cells.Both ionizing radiation and most chemotherap...

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“…To assemble the oligo-thiazoline, several alternatives were worked out. The group of Pattenden successfully established an iterative condensation of nitriles with 2-methylcysteine to extend the chain C-terminally [16]. In a potentially more biomimetic variant, Heathcock showed that a string of 2-methylcysteines can be condensed to an oligothiazole with considerable efficiency.…”

Section: Thiangazolementioning

confidence: 99%

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

Arndt

Lichtenecker

Loos

et al. 2011

Biomimetic Organic Synthesis

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Total synthesis of thiangazole, a novel naturally occurring HIV-1 inhibitor from Polyangium sp

Cited by 58 publications

References 20 publications

Solvent‐Free Tandem Synthesis of 2‐Thiazolines and 2‐Oxazolines Catalyzed by a Copper Catalyst

Solvent‐Free Tandem Synthesis of 2‐Thiazolines and 2‐Oxazolines Catalyzed by a Copper Catalyst

Gold nanoparticles as a platform for creating a multivalent poly-SUMO chain inhibitor that also augments ionizing radiation

Biomimetic Synthesis of Azole‐ and Aryl‐Peptide Alkaloids

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