Tide Quenchers™ (TQ)

Classic dark quenchers like DABCYL have long-standing use in FRET applications, but limitations such as narrower spectral coverage, environment-sensitive absorption, and reduced quenching efficiency for some longer-wavelength fluorophores can compromise assay sensitivity in certain applications.

Tide Quencher™ Dark FRET Acceptors

Tide Quenchers™ span the entire visible and near-infrared spectrum (450–880 nm) and are designed to provide high quenching efficiency across this range. Each quencher is individually optimized to match specific fluorophore emission profiles: TQ2 is well matched to FAM, HEX, TET, and JOE; TQ3 provides superior performance with TAMRA and Cy3®; TQ5 series quenches Cy5® and Alexa Fluor® 647; and TQ7/TQ8 extend coverage into the NIR range for Cy7® and ICG applications. Compared to classic quenchers, Tide Quenchers offer stronger molar absorption coefficients and higher quenching efficiency, resulting in complete substrate quenching with minimal background from non-specific acceptor excitation.

Feature	Benefit
Higher Absorption Coefficients	Stronger energy transfer for more efficient quenching
Superior Quenching Efficiency	Lower background fluorescence than DABCYL, BHQ, and QSY dyes
Environment-Insensitive	Consistent performance across pH and buffer conditions
Full Spectral Coverage	TQ1–TQ8 spans 450 nm to 880 nm (visible through IR)
Enhanced Water Solubility	WS and HWS versions for aqueous assays without organic solvents
Versatile Reactive Forms	Acid, NHS ester, maleimide, azide, alkyne, DBCO, CPG, phosphoramidite
Cost-Effective	Competitive pricing with better performance

Fig. 1

Absorbance spectra of Tide Quencher™ non-fluorescent dyes.

Optimized FRET Pairs for Tide Quenchers™

Effective FRET requires spectral overlap between donor emission and acceptor absorption. Tide Quencher™ dyes are precisely tuned to match the emission spectra of Tide Fluor™ (TF) donors and classic fluorophores including EDANS, FAM, TAMRA, ROX, HEX, JOE, TET, and the Cy® dye series. This optimization ensures maximum quenching efficiency in the intact probe and strong signal recovery upon cleavage.

The tables below can be used to determine the optimal Tide Quencher™ to pair with a particular donor fluorophore as well as which classic quenchers can be upgrade to Tide Quenchers™.

Reactive Form Selection Guide for Tide Quenchers™

Tide Quenchers™ are available in multiple reactive forms to accommodate different conjugation chemistries:

Reactive Form	Target Group	Best For	Conditions
Acid	Amines (via EDC/carbodiimide)	Peptides, reference standards	Aqueous, pH 4–6
NHS Ester (SE)	Primary amines (–NH₂)	Amino-modified oligos, Lys, N-terminus	pH 7–9, avoid Tris buffer
Maleimide	Thiols (–SH)	Cys residues, thiol-modified oligos	pH 6.5–7.5
Amine	Carbonyls (aldehydes, ketones)	Reductive amination	Reducing agent required
Azide	Alkynes, DBCO	Click chemistry (CuAAC, SPAAC)	Copper catalyst or strain-promoted
Alkyne	Azides	Click chemistry (CuAAC)	Copper catalyst required
DBCO	Azides	Copper-free click chemistry (SPAAC)	Physiological conditions
CPG (500Å/1000Å)	—	In-synthesis oligo labeling	Automated DNA synthesizer
Phosphoramidite	—	In-synthesis oligo labeling	Automated DNA synthesizer

Tide Quencher™ Solubility Variants

Standard Tide Quenchers™ are suitable for most organic synthesis and conjugation workflows. Water-soluble (WS) versions incorporate sulfonate groups that dramatically improve aqueous solubility, reduce aggregation, and minimize non-specific interactions in biological assays.

WS variants are particularly recommended when:

Working in strictly aqueous buffer systems
Labeling hydrophobic peptide sequences (TQ-WS conjugation can enhance peptide solubility)
Performing live-cell applications
Minimizing organic solvent use in conjugation reactions

The newer HWS (highly water-soluble) variants—including TQ3HWS, TQ5HWS, and TQ7HWS—offer even greater hydrophilicity for the most demanding aqueous applications.

Tide Fluor™ and Tide Quencher™ M/Z Values

M/Z (mass-to-charge ratio) values are used to confirm the identity of molecules via mass spectrometry. The M/Z values listed below represent the expected molecular ions for each Tide Fluor™ and Tide Quencher™ dye. These reference values can be used to verify successful conjugation when attaching dyes to peptides, oligonucleotides, or other biomolecules—ensuring the correct fluorophore or quencher is incorporated and the final construct has the expected mass.

Tide Quencher™-labeled FMOC-Amino Acid Building Blocks

Pre-labeled FMOC-amino acids streamline solid-phase peptide synthesis (SPPS) of FRET substrates. These building blocks—available as FMOC-Lys, FMOC-Glu, and FMOC-Asp derivatives with TQ2 or TQ3—eliminate post-synthetic labeling steps and ensure consistent, high-purity products for protease assay development.

Applications

Molecular Diagnostics & qPCR

Tide Quenchers™ are ideal for nucleic acid detection assays where low background and high signal-to-noise ratios are critical. The quencher suppresses fluorescence until a specific event—such as probe cleavage, strand separation, or primer extension—results in an increase in donor fluorescence for quantification.

TaqMan® Probes — Dual-labeled hydrolysis probes for real-time PCR
Molecular Beacons — Hairpin probes for SNP detection and gene expression
Scorpion Primers — Self-probing amplification primers

Protease & Enzyme Assays

FRET peptide substrates incorporating Tide Quenchers™ enable sensitive detection of protease activity. Enzyme hydrolysis spatially separates the donor and quencher, restoring fluorescence for quantification. These substrates are widely used in drug discovery screening campaigns.

FRET Peptide Substrates — HIV protease, MMPs, secretases, caspases
High-Throughput Screening — Drug discovery and enzyme kinetics

Oligonucleotide Labeling

Multiple labeling strategies accommodate both automated synthesis and post-synthetic modification workflows.

In-Synthesis Labeling — CPG (500 Å and 1000 Å pore sizes) and phosphoramidite reagents for automated synthesis
Post-Synthetic Labeling — NHS esters for amino-modified oligos, maleimides for thiol-modified oligos

This document (01.0072.211015r2) was last updated on Tue Feb 17 2026. All trademarks and registered trademarks mentioned herein are the property of their respective owners.