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Ligases

Catalog Product Name EC No. CAS No. Source Price
DIA-433 Glutamine Synthetase (GST) from Microorganism EC 6.3.1.2 Microorganism Inquiry
DIA-544 High Purity Succinyl Coenzyme A Synthetase EC 6.2.1.5 9080-33-5 Prokaryote Inquiry
DIA-881 T4RNA Ligase EC 6.5.1.3 Inquiry
NATE-1712 Acyl-CoA synthetase from Microorganism EC 6.2.1.3 9013-18-7 Microorganism Inquiry
Nucleic-acid joining enzymes for molecular diagnostic workflows

Ligases

Ligases form covalent bonds between compatible nucleic-acid ends. Their performance in library preparation, probe assembly, circularization, and junction detection depends on end chemistry, substrate structure, cofactor system, and control of unwanted ligation products.

What ligases contribute to molecular assays

DNA and RNA ligases seal a phosphodiester bond between a 3′ hydroxyl and a 5′ phosphate, but they differ in substrate preference, cofactor use, temperature range, and tolerance for mismatched or structured junctions. A ligase chosen for rapid cloning is not automatically suitable for adapter ligation or a sequence-discrimination assay.

The useful output is the correct junction, not simply a high amount of joined material. Adapter dimers, self-ligated probes, concatemers, and off-target products can consume reagents and reduce the fraction of molecules that enter amplification or sequencing. Product yield and product identity therefore need to be measured together.

Start with the junction: define whether the substrate is DNA or RNA, single- or double-stranded, blunt or overhanging, phosphorylated or adenylated, and sequence-matched or mismatch-sensitive.

Adapter ligation

Ligases attach adapters to DNA or RNA so molecules can be amplified, indexed, captured, or sequenced.

Probe circularization

A correctly hybridized probe can be sealed into a circle for rolling-circle amplification or other closed-template workflows.

Junction discrimination

Thermostable ligases can support assays in which ligation occurs preferentially at a correctly matched target junction.

End repair and assembly

Ligation can complete a multi-enzyme end-repair or assembly workflow after termini have been prepared to the required chemistry.

Ligase types and their practical differences

Ligase selection begins with nucleic-acid type and junction structure. Temperature, ATP or NAD dependence, sequence context, and downstream workflow then separate candidates within that group.

T4 DNA ligase

A widely used ATP-dependent enzyme for sealing nicks and joining compatible DNA ends in assembly and library workflows.

Check: end phosphorylation, adapter concentration, and self-ligation.

Thermostable DNA ligases

Ligases such as Taq DNA ligase operate at elevated temperatures and can support cycling or stringent junction recognition.

Check: NAD dependence, mismatch position, and cycling conditions.

T4 RNA ligase 1

This ATP-dependent enzyme joins single-stranded RNA termini and can also ligate selected oligonucleotide substrates.

Check: RNA structure, end chemistry, and sequence bias.

Pre-adenylated or ATP-independent workflows

Using an activated donor can reduce ATP-driven adapter dimer formation in selected library designs.

Check: donor adenylation state and enzyme compatibility.

Specialized circularization ligases

Substrate-specific enzymes may favor single-stranded DNA or RNA circularization under defined conditions.

Check: minimum length, secondary structure, and circular product confirmation.

Ligase junction and end-chemistry selectorFig 1. Ligase junction and end-chemistry selector.
(Creative Enzymes Diagnostic)

How to select a ligase

Use substrates that reproduce the intended ends, modifications, sequence context, and concentration. A generic nick-sealing assay does not reveal adapter bias or mismatch discrimination.

Selection factorHow to evaluate itWhy it matters
Nucleic-acid type and structureDefine DNA or RNA, strand state, length, secondary structure, and whether the junction is intramolecular or intermolecular.Ligases differ substantially in their ability to access and join structured or single-stranded substrates.
End chemistryConfirm 5′ phosphorylation or adenylation, 3′ hydroxyl availability, overhang type, and terminal modifications.Incorrect end chemistry prevents the desired phosphodiester bond even when the enzyme is active.
Cofactor and buffer systemTest ATP or NAD, magnesium, salts, reducing agents, crowding agents, and additives together.The cofactor system controls catalysis and can also influence side products and downstream reactions.
Temperature and mismatch behaviorMeasure correct and incorrect junctions across the planned temperature or cycling profile.Stringency depends on duplex stability, mismatch position, sequence, and ligase kinetics.
Desired product and artifactsQuantify the correct junction, adapter dimers, concatemers, and unligated material with a suitable analytical method.Total ligated material can look high while usable library or probe product remains low.
Downstream compatibilityCarry ligated material into amplification, reverse transcription, sequencing, or detection without changing the cleanup strategy.Residual enzyme, ATP, salts, and side products may reduce performance after ligation.

Library-preparation ligation decision pathFig 2. Library-preparation ligation decision path.
(Creative Enzymes Diagnostic)

Selected Creative Enzymes ligases

Creative Enzymes supplies DNA and RNA ligases for molecular assay research, library preparation, and reagent development. Select a product name to review the corresponding information.

ProductCatalogEC numberSourceActivity
T4 RNA Ligase 1DIA-576
Taq DNA LigaseDIA-578
T4 DNA Ligase (Rapid)DIA-584Escherichia coli

Activity values use product-specific assay definitions. Review the stated method and test conditions before comparing unit values across materials.

Qualifying ligation for the intended workflow

A useful ligation process must deliver the correct junction reproducibly and leave the material compatible with the next step. Qualification should therefore follow the substrate from input through downstream detection.

Define the substrate population

Describe termini, modifications, strand state, sequence diversity, concentration, and expected secondary structure.

Optimize junction formation

Screen enzyme, cofactor, temperature, time, and substrate ratios while measuring the intended junction and major artifacts.

Test the downstream step

Evaluate amplification, reverse transcription, sequencing, or probe detection using the same cleanup and carryover conditions planned for the assay.

Control manufacturing variation

Establish incoming activity, formulation limits, storage, freeze–thaw handling, lot bridging, and an application-relevant release method.

Ligation artifact control mapFig 3. Ligation artifact control map.
(Creative Enzymes Diagnostic)

Information to include with an inquiry

Provide the nucleic-acid type, sequences or diversity, end chemistry, substrate concentration, desired junction, temperature profile, cofactor constraints, acceptable artifacts, downstream workflow, format, and scale.

Frequently asked questions

What is the first question when selecting a ligase?

Define the nucleic-acid type and exact end chemistry. A 5′ phosphate, 3′ hydroxyl, pre-adenylated donor, blunt end, or overhang can require a different ligation strategy.

Why can high ligation yield still give poor assay performance?

The measured material may include adapter dimers, concatemers, or incorrect junctions. Product identity must be assessed together with total conversion.

When is a thermostable ligase useful?

It is useful when elevated temperature or thermal cycling improves junction stringency, but the intended sequence and mismatch panel must be tested directly.

How should an RNA ligase be evaluated?

Test the actual RNA termini, secondary structures, sequence diversity, adapter ratio, ATP condition, and compatibility with the next enzymatic step.

Can ligase activity be compared by unit value alone?

Not reliably. Unit assays may use different substrates and endpoints. Compare enzymes with a common junction-specific method under application conditions.

What information should be confirmed before scale-up?

Confirm activity definition, formulation, cofactor requirements, storage, freeze–thaw limits, acceptable artifact profile, and lot-to-lot functional performance.

Selected scientific and institutional references

These sources support the scientific classification and technical selection criteria. Product specifications must be confirmed in current Creative Enzymes documentation.

  1. IUBMB enzyme nomenclature and classification
  2. NC-IUBMB rules for enzyme classification

Online Inquiry

For research and industrial use only, not for personal medicinal use.

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