Unnatural Rigid Scaffolds Targeting the Bacterial Ribosome

Katsoulis, Ioannis A.; Pyrkotis, Constantina; Papakyriakou, Athanasios; Kythreoti, Georgia; Zografos, Alexandros L.; Mavridis, Irene M.; Nahmias, Victoria R.; Αναστασοπούλου, Πανούλα; Vourloumis, Dionisios

doi:10.1002/cbic.200900268

Cited by 8 publications

(1 citation statement)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[26] Thus, new chemical entities locked in the ribosome-bound "bioactive" conformation in which the glycosidic bond has been replaced by a rigid quaternary center, were targeted (I, Scheme 1). [27] Secondly, the conservation of established contacts between natural aminoglycosides and the A-site RNA [28] represents a major priority of our design. Specifically, key characteristic interactions that we attempted to maintain (shown in Figure 1 A for neamine) are: 1) The formation of a pseudo base pair with A1408; 2) The contacts with O4 of U1495; 3) The contact with N7 of G1494; and 4) The contacts with the phosphate group of A1492, A1493, and G1494.…”

Section: Introductionmentioning

confidence: 99%

Designed Spiro‐Bicyclic Analogues Targeting the Ribosomal Decoding Center

et al. 2010

Self Cite

View full text Add to dashboard Cite

The bacterial ribosome represents the confirmed biological target for many known antibiotics that interfere with bacterial protein synthesis. Aminoglycosides represent a lead paradigm in RNA molecular recognition and constitute ideal starting points for the design and synthesis of novel RNA binders. Previous rational design approaches of RNA-targeting small molecules have been mainly concentrated on direct functionalization of aminoglycosidic substructures. Herein, we successfully designed and synthesized rigid spirocyclic scaffolds locked in a predicted ribosome-bound "bioactive" conformation. These analogues are able to mimic many of the interactions of the natural products for the A-site, as proven by their obtained binding affinities. The development of an optimized approach for their synthesis and their potential to inhibit protein production in vitro are presented. Our results could be further utilized for the development of analogues with improved antibiotic profiles.

show abstract

Section: Introductionmentioning

confidence: 99%

Designed Spiro‐Bicyclic Analogues Targeting the Ribosomal Decoding Center

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

Synthesis of 5,6‐Spiroethers and Evaluation of their Affinities for the Bacterial A Site

Katsoulis¹,

Kythreoti²,

Papakyriakou³

et al. 2011

ChemBioChem

Self Cite

View full text Add to dashboard Cite

show abstract

Concise Stereoselective Synthesis of Oxaspirocycles with 1‐Tosyl‐1,2,3‐triazoles: Application to the Total Syntheses of (±)‐Tuberostemospiroline and (±)‐Stemona‐lactam R

Shen

Chang

et al. 2014

Chemistry A European J

View full text Add to dashboard Cite

A 4-substituted-1-tosyl-1,2,3-triazole-based stereoselective synthesis of structurally diverse oxaspirocycles is reported. The synthesis involves Rh-catalyzed loss of nitrogen from 4-substituted-1-tosyl-1,2,3-triazoles, Grignard reaction, and a ring-closing metathesis reaction as key steps. By employing readily available and stable 4-substituted-1-tosyl-1,2,3-triazoles as surrogates of diazo compounds and nitrogen sources, two types of oxaspirocycles were obtained. The latter compounds, which contain adjacent nitrogen stereocenters, could serve as the core structures of many natural products. This chemistry has been successfully applied to the total syntheses of (±)-tuberostemospiroline and (±)-stemona-lactam R.

show abstract

Unnatural Rigid Scaffolds Targeting the Bacterial Ribosome

Cited by 8 publications

References 32 publications

Designed Spiro‐Bicyclic Analogues Targeting the Ribosomal Decoding Center

Designed Spiro‐Bicyclic Analogues Targeting the Ribosomal Decoding Center

Synthesis of 5,6‐Spiroethers and Evaluation of their Affinities for the Bacterial A Site

Concise Stereoselective Synthesis of Oxaspirocycles with 1‐Tosyl‐1,2,3‐triazoles: Application to the Total Syntheses of (±)‐Tuberostemospiroline and (±)‐Stemona‐lactam R

Contact Info

Product

Resources

About