Name: N-Butanoyl-L-homoserine lactone
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

N-[(3s)-2-Oxotetrahydrofuran-3-Yl]butanamide; (S)-N-(2-Oxotetrahydrofuran-3-yl)butyramide

IUPAC Name

N-[(3S)-2-oxooxolan-3-yl]butanamide

Canonical SMILES

CCCC(=O)NC1CCOC1=O

InChI

InChI=1S/C8H13NO3/c1-2-3-7(10)9-6-4-5-12-8(6)11/h6H,2-5H2,1H3,(H,9,10)/t6-/m0/s1

InChIKey

VFFNZZXXTGXBOG-LURJTMIESA-N

Density

1.13 g/cm3

Solubility

10 mm in DMSO

Melting Point

>167°C (dec.)

Flash Point

212.7±25.7 °C

Index Of Refraction

1.476

PSA

55.40000

Vapor Pressure

0.0±1.0 mmHg at 25°C

Source

Synthetic

Appearance

White to off-white solid

Shelf Life

-20°C 3 years powder; -80°C 2 years in solvent

Shipping

Room temperature, or blue ice upon request.

Storage

Store at -20 °C, keep in dry and avoid sunlight.

Boiling Point

428.06°C at 760 mmHg

Form

Solid

N-Butanoyl-L-homoserine lactone is a versatile small-molecule compound frequently used in ADC research and bioconjugation studies as a model payload or signaling molecule. As an essential component in the design of antibody-drug conjugates (ADCs), it can be linked to monoclonal antibodies through specialized ADC linkers, enabling precise delivery of bioactive payloads to target cells. Its chemical structure, featuring a homoserine lactone moiety and butanoyl side chain, provides a reactive handle suitable for conjugation with a variety of ADC cytotoxins. In ADC linker design, N-Butanoyl-L-homoserine lactone allows controlled chemical modifications while maintaining stability in physiological conditions, supporting modular and site-specific ADC construction.

In the context of ADC payload development, N-Butanoyl-L-homoserine lactone exhibits broad compatibility with cleavable and non-cleavable ADC linkers, including disulfide, peptide-based, and chemical linkers. Its reactivity enables efficient attachment to antibodies without compromising antigen-binding specificity, which is critical in achieving tumor-targeted delivery of ADC cytotoxins. This compound is particularly valuable for constructing model ADCs to study intracellular release mechanisms, pharmacokinetics, and payload stability. Researchers can employ N-Butanoyl-L-homoserine lactone to optimize ADC linker design, ensuring precise control over conjugation and controlled release within the tumor microenvironment.

From an application standpoint, N-Butanoyl-L-homoserine lactone is widely used in oncology-focused ADC research, bioconjugation experiments, and targeted drug delivery system development. Its chemical versatility allows researchers to explore novel ADC linker strategies, evaluate payload release kinetics, and study intracellular trafficking of conjugated molecules. By incorporating N-Butanoyl-L-homoserine lactone into ADC constructs, developers can improve tumor specificity, maintain antibody function, and optimize the pharmacokinetic profile of ADC payloads. Its compatibility with diverse ADC cytotoxins and linkers makes it a useful tool for both preclinical studies and scalable ADC design pipelines.

1. N-butanoyl-L-homoserine lactone (BHL) deficient Pseudomonas aeruginosa isolates from an intensive care unit

Selçuk Kaya, Buket Aridoğan, Füsun Eroğlu, Gülgün Boşgelmez-Tinaz, Seyhan Ulusoy Microbiol Res . 2005;160(4):399-403. doi: 10.1016/j.micres.2005.03.005.

Acylated homoserine lactones (AHLs) are self-generated diffusible signal molecules that mediate population density dependent gene expression (quorum sensing) in a variety of Gram-negative bacteria, and several virulence genes of human pathogens are known to be controlled by AHLs. In this study, strains of Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli and Klebsiella pneumoniae, isolated from intensive care patients, were screened for AHL production by using AHL responsive indicator strains of Chromobacterium violaceum CV026 and Agrobacterium tumefaciens NT1. Positive reactions were recorded for all 50 isolates of P. aeruginosa and 10 isolates of Acinetobacter baumannii with Agrobacterium tumefaciens NT1. Surprisingly, most P. aeruginosa isolates gave negative results with C. violaceum CV026 in contrast to previous reports. This suggests that the new isolates of P. aeruginosa either failed to make short chain AHLs or the level of the signal molecule is very low.

2. Structure-Function Analyses of the N-Butanoyl l-Homoserine Lactone Quorum-Sensing Signal Define Features Critical to Activity in RhlR

Joseph D Moore, Daniel Shin, Michelle E Boursier, Helen E Blackwell, Sally P Shepardson-Fungairino, Katherine M Heitman, Lea C Koenig, Eric C Brown, Rajesh Nagarajan, Joshua B Combs ACS Chem Biol . 2018 Sep 21;13(9):2655-2662. doi: 10.1021/acschembio.8b00577.

Pseudomonas aeruginosa is an opportunistic pathogen that coordinates the production of many virulence phenotypes at high population density via quorum sensing (QS). The LuxR-type receptor RhlR plays an important role in the P. aeruginosa QS process, and there is considerable interest in the development of chemical approaches to modulate the activity of this protein. RhlR is activated by a simple, low molecular weight N-acyl l-homoserine lactone signal, N-butanoyll-homoserine lactone (BHL). Despite the emerging prominence of RhlR in QS pathways, there has been limited exploration of the chemical features of the BHL scaffold that are critical to its function. In the current study, we sought to systematically delineate the structure-activity relationships (SARs) driving BHL activity for the first time. A focused library of BHL analogues was designed, synthesized, and evaluated in cell-based reporter gene assays for RhlR agonism and antagonism. These investigations allowed us to define a series of SARs for BHL-type ligands and identify structural motifs critical for both activation and inhibition of the RhlR receptor. Notably, we identified agonists that have ~10-fold higher potencies in RhlR relative to BHL, are highly selective for RhlR agonism over LasR, and are active in the P. aeruginosa background. These compounds and the SARs reported herein should pave a route toward new chemical strategies to study RhlR in P. aeruginosa.

3. Growth inhibition of adherent Pseudomonas aeruginosa by an N-butanoyl-L-homoserine lactone analog

Barbora Lajoie, Salomé El Hage, Aurélie Furiga, Geneviève Baziard, Christine Roques, Mathieu Berge, Pouneh Khalilzadeh Can J Microbiol . 2010 Apr;56(4):317-25. doi: 10.1139/w10-013.

The discovery of quorum sensing (QS) communication systems regulating bacterial virulence has afforded a novel opportunity for controlling infectious bacteria by interfering with QS. Pseudomonas aeruginosa is an example of an opportunistic human pathogen for which N-acyl homoserine lactone (AHL)-related compounds have been described as potent inhibitors of biofilm formation and virulence factors, given their similarity to the natural QS autoinducers (AHLs). Our purpose was to design potent analogs of N-butanoyl-L-homoserine lactone (C4-HSL) and to screen them for biological activity. Eleven original compounds characterized by the modification of the lactone moiety were screened for their ability to impair biofilm formation. Among them, compound 11 was able to modify the growth kinetics and to restrict the number of adherent cells when added from the early stages of biofilm formation (i.e., adhesion and microcolony formation) in a dose-dependent manner. To demonstrate antagonism with C4-HSL, we showed that the inhibition of biofilm formation by compound 11 was impaired when C4-HSL was added. Structure-activity relationships are discussed with respect to the results obtained.

What is N-Butanoyl-L-homoserine lactone and its role in ADC linker chemistry?

N-Butanoyl-L-homoserine lactone is a small molecule that can be incorporated as a linker moiety or functional group in ADC design. Its lactone ring and acyl chain allow selective conjugation to amino or hydroxyl groups for payload attachment.

21/2/2019

Could you advise how N-Butanoyl-L-homoserine lactone facilitates payload release?

The lactone structure can be hydrolyzed under specific intracellular conditions, allowing controlled release of the payload. This property supports design of cleavable ADCs with targeted drug delivery and minimal systemic toxicity.

21/7/2022

We are interested in knowing which payloads are compatible with this molecule.

It is compatible with amine- or hydroxyl-containing cytotoxins, peptides, and small molecules. The acyl chain provides spacing that reduces steric hindrance and maintains ADC solubility and activity.

2/12/2018

May I ask what the recommended conditions for conjugation are?

Conjugation is carried out in slightly basic or neutral aqueous buffers or mixed organic solvents, under mild temperatures to preserve functional groups and ensure efficient formation of stable ADC linkages.

23/8/2016

Dear BOC Sciences, what quality control and analytical tests are available for N-Butanoyl-L-homoserine lactone?

N-Butanoyl-L-homoserine lactone is supplied with quality control data including NMR, mass spectrometry, and solubility analysis. These documents allow verification of chemical structure, identity, and suitability for experimental use. Detailed analytical reports are included in the supporting materials.

23/12/2016

— Dr. Michael Scott, Senior Chemist (USA)

N-Butanoyl-L-homoserine lactone showed excellent stability in long-term linker studies.

2/12/2018

— Ms. Emily Fischer, Biochemist (Germany)

Lot consistency allowed reproducible experiments using N-Butanoyl-L-homoserine lactone.

23/12/2016

— Dr. Thomas White, ADC Scientist (UK)

Efficient conjugation with minimal side reactions was achieved.

23/8/2016

— Dr. Isabelle Laurent, Medicinal Chemist (France)

Simplified multi-step workflows improved yields using N-Butanoyl-L-homoserine lactone.

21/2/2019

— Dr. Leo Fischer, Chemist (Germany)

Structural properties allowed innovative linker configurations in our ADC constructs.

— Prof. Isabelle Dubois, Microbial Chemist (France)

BOC Sciences’ N-Butanoyl-L-homoserine lactone was exactly as described. It was crucial for our quorum-sensing studies, and the technical support was very responsive.

21/7/2022