Dataset Information

Synthesis of 9-Substituted Triptycene Building Blocks for Solid-Phase Diversification and Nucleic Acid Junction Targeting.

ABSTRACT: Triptycenes have been shown to bind nucleic acid three-way junctions, but rapid and efficient methods to diversify the triptycene core are lacking. An efficient synthesis of a 9-substituted triptycene scaffold is reported that can be used as a building block for solid-phase peptide synthesis and rapid diversification. The triptycene building block was diversified to produce a new class of tripeptide-triptycenes, and their binding abilities toward d(CAG)·(CTG) repeat junctions were investigated.

SUBMITTER: Yoon I

PROVIDER: S-EPMC5106869 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthesis of 9-Substituted Triptycene Building Blocks for Solid-Phase Diversification and Nucleic Acid Junction Targeting.

Yoon Ina I Suh Sung-Eun SE Barros Stephanie A SA Chenoweth David M DM

Organic letters 20160217 5

Triptycenes have been shown to bind nucleic acid three-way junctions, but rapid and efficient methods to diversify the triptycene core are lacking. An efficient synthesis of a 9-substituted triptycene scaffold is reported that can be used as a building block for solid-phase peptide synthesis and rapid diversification. The triptycene building block was diversified to produce a new class of tripeptide-triptycenes, and their binding abilities toward d(CAG)·(CTG) repeat junctions were investigated. ...[more]

PMID: 26886290

Similar Datasets

Project description:As a key cytokine mediator of inflammation, interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and activates various downstream signaling mediators, including NF-κB, which is required for immune vigilance and cellular protection. Toward the development of IL-1-targeting therapeutics which exhibit functional selectivity, the all-D-amino acid peptide 1 (101.10, H-D-Arg-D-Tyr-D-Thr-D-Val-D-Glu-D-Leu-D-Ala-NH2) was conceived as an allosteric IL-1R modulator that conserves NF-κB signaling while inhibiting other IL-1-activated pathways. Employing β-hydroxy-α-amino-γ-lactam (Hgl) stereoisomers to study the conformation about the Thr3 residue in 1, [(3R,4S)-Hgl3]-1 (2b), among all possible diastereomers, was found to exhibit identical in vitro and in vivo activity as the parent peptide and superior activity to the α-amino-γ-lactam (Agl) counterpart. Noting the relevance of the β-hydroxyl substituent and configuration for the activity of (3R,4S)-2b, fifteen different β-substituted-Agl3 analogs of 1 (e.g., 2c-q) have now been synthesized by a combination of solution- and solid-phase methods employing N-Fmoc-β-substituted-Agl3-Val-OH dipeptide building blocks. Introduction of a β-azido-Agl3 residue into the resin bound peptide and subsequent reduction and CuAAC chemistry gave access to a series of amine and triazole derivatives (e.g., 2h-q). β-Substituted-[Agl3]-1 analogs 2c-q exhibited generally similar circular dichroism (CD) spectra as that of Hgl analog 2b in water, presenting curve shapes indicative of β-turn structures. The relevance of the β-substituent was indicated in rodent models of preterm labor and retinopathy of prematurity (ROP), in which certain analogs inhibited preterm birth and vaso-obliteration, respectively, with activity similar to 1 and 2b. The β-substituted-[Agl3]-1 analogs exhibited functional selectivity on IL-1-induced signaling pathways. The described solid-phase method has provided discerning probes for exploring peptide structure-activity relationships and valuable leads for developing prototypes to treat inflammatory events leading to prematurity and retinopathy of prematurity, which are leading causes of infant morbidity and blindness respectively.

Dataset Information

Synthesis of 9-Substituted Triptycene Building Blocks for Solid-Phase Diversification and Nucleic Acid Junction Targeting.

Publications

Synthesis of 9-Substituted Triptycene Building Blocks for Solid-Phase Diversification and Nucleic Acid Junction Targeting.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets